Protein kinase modulators and methods of use

ABSTRACT

This invention relates to compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion, and to pharmaceutical compositions containing such compounds. Even more specifically, the invention relates to compounds that inhibit, regulate and/or modulate kinases, particularly Checkpoint Kinases, even more particularly Checkpoint Kinase 1, or Chk1. Methods of therapeutically or prophylactically using the compounds and compositions to treat kinase-dependent diseases and conditions are also an aspect of the invention, and include methods of treating cancer, as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, by administering effective amounts of such compounds.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to compounds for modulating protein kinaseenzymatic activity for modulating cellular activities such asproliferation, differentiation, programmed cell death, migration andchemoinvasion, and to pharmaceutical compositions containing suchcompounds. Even more specifically, the invention relates to compoundsthat inhibit, regulate and/or modulate kinases, particularly CheckpointKinases, even more particularly Checkpoint Kinase 1, or Chk1. Methods oftherapeutically or prophylactically using the compounds and compositionsto treat kinase-dependent diseases and conditions are also an aspect ofthe invention, and include methods of treating cancer, as well as otherdisease states associated with unwanted angiogenesis and/or cellularproliferation, by administering effective amounts of such compounds.

2. Summary of Related Art

Cells reproduce by duplicating their contents and then dividing in two.This cell division cycle is the fundamental means by which all livingthings are propagated. In unicellular species, such as bacteria andyeasts, each cell division produces an additional organism. Inmulticellular species many rounds of cell division are required to makea new individual, and cell division is needed in the adult body too, toreplace cells that are lost by wear and tear or by programmed celldeath. Thus an adult human must manufacture many millions of new cellseach second simply to maintain the status quo, and if all cell divisionis halted—for example, by a large dose of ionizing radiation—theindividual will die within a few days.

The cell division cycle is the subject of a control system thatcoordinates the cycle as a whole. A multitude of genes, proteins andother cellular machinery directly or indirectly regulate progression ofa cell through the cell division cycle. Regulatory elements can eitherhelp stimulate an increase in cell numbers or help to inhibit it.Uncontrolled cell proliferation is the insignia of cancer, and can bemanifested by a deregulation of the cell division cycle in one of twoways—making stimulatory genes hyperactive or inhibitory genes inactive.

It can be understood, therefore, that agents that modulate the cellcycle, and thus hyperproliferation, could be used to treat variousdisease states associated with uncontrolled or unwanted cellproliferation. In addition to oncological indications, altered cellcycle division signaling is implicated in numerous other pathologicaldiseases. These include, but are not limited to antiparasitics (See,Gray et al., Curr. Med. Chem. 6, 859-875 (1999)); potential antivirals(See, Schang et al., J. Virol. 74, 2107-2120 (2000)); cardiovascularmaladies such as artherosclerosis or restenosis (See Braun-Dullaeus etal., Circulation, 98, 82-89 (1998)); and states of inflammation andimmunological disorders, such as arthritis (See, Taniguchi et al.,Nature Med., 5, 760-767(1999)) or psoriasis.

Mechanisms of cell proliferation are under active investigation atcellular and molecular levels. At the cellular level, de-regulation ofsignaling pathways, loss of cell cycle controls, unbridled angiogenesisor stimulation of inflammatory pathways are under scrutiny, while at themolecular level, these processes are modulated by various proteins,among which protein kinases are prominent suspects. Overall abatement ofproliferation may also result from programmed cell death, or apoptosis,which is also regulated via multiple pathways, some involvingproteolytic enzyme proteins. Among the candidate regulatory proteins,protein kinases are a family of enzymes that catalyze phosphorylation ofproteins, in particular the hydroxyl group of specific tyrosine, serine,or threonine residues in proteins. The consequences of this seeminglysimple activity are staggering, and typically, such phosphorylationdramatically perturbs the function of the protein, and thus proteinkinases are pivotal in the regulation of a wide variety of cellularprocesses, including metabolisim, cell proliferation, celldifferentiation, and cell survival. Of the many different cellularfunctions in which the activity of protein kinases is known to berequired, some processes represent attractive targets for therapeuticintervention for certain disease states. Two examples are cell-cyclecontrol and angiogenesis, in which protein kinases play a pivotal role;these processes are essential for the growth of solid tumors as well asfor other diseases.

CDKs constitute a class of enzymes that play critical roles inregulating the transitions between different phases of the cell cycle,such as the progression from a quiescent stage in G.sub.1 (the gapbetween mitosis and the onset of DNA replication for a new round of celldivision) to S (the period of active DNA synthesis), or the progressionfrom G.sub.2 to M phase, in which active mitosis and cell-divisionoccur. See, e.g., the articles compiled in Science, vol. 274 (1996), pp.1643-1677; and Ann. Rev. Cell Dev. Biol., vol. 13 (1997), pp. 261-291.CDK complexes are formed through association of a regulatory cyclinsubunit (e.g., cyclin A, B1, B2, D1, D2, D3, and E) and a catalytickinase subunit (e.g., cdc2 (CDK1), CDK2, CDK4, CDK5, and CDK6). As thename implies, the CDKs display an absolute dependence on the cyclinsubunit in order to phosphorylate their target substrates, and differentkinase/cyclin pairs function to regulate progression through specificportions of the cell cycle.

The D cyclins are sensitive to extracellular growth signals and becomeactivated in response to mitogens during the G.sub.1 phase of the cellcycle. CDK4/cyclin D plays an important role in cell cycle progressionby phosphorylating, and thereby inactivating, the retinoblastoma protein(Rb). Hypophosphorylated Rb binds to a family of transcriptionalregulators, but upon hyperphosphorylation of Rb by CDK4/cyclin D, thesetranscription factors are released to activate genes whose products areresponsible for S phase progression. Rb phosphorylation and inactivationby CDK4/cyclin D permit passage of the cell beyond the restriction pointof the G.sub.1 phase, whereupon sensitivity to extracellular growth orinhibitory signals is lost and the cell is committed to cell division.During late G.sub.1, Rb is also phosphorylated and inactivated byCDK2/cyclin E, and recent evidence indicates that CDK2/cyclin E can alsoregulate progression into S phase through a parallel pathway that isindependent of Rb phosphorylation (see Lukas et al., “Cyclin E-induced SPhase Without Activation of the pRb/E2F Pathway,” Genes and Dev., vol.11 (1997), pp. 1479-1492).

The progression from G.sub.1 to S phase, accomplished by the action ofCDK4/cyclin D and CDK2/cyclin E, is subject to a variety of growthregulatory mechanisms, both negative and positive. Growth stimuli, suchas mitogens, cause increased synthesis of cyclin D1 and thus increasedfunctional CDK4. By contrast, cell growth can be “reined in,” inresponse to DNA damage or negative growth stimuli, by the induction ofendogenous inhibitory proteins. These naturally occurring proteininhibitors include p.sub.21.sup.WAF1/CIP1, p27.sup.KIP1, and thep16.sup.INK4 family, the latter of which inhibit CDK4 exclusively (seeHarper, “Cyclin Dependent Kinase Inhibitors,” Cancer Surv., vol. 29(1997), pp. 91-107). Aberrations in this control system, particularlythose that affect the function of CDK4 and CDK2, are implicated in theadvancement of cells to the highly proliferative state characteristic ofmalignancies, such as familial melanomas, esophageal carcinomas, andpancreatic cancers (see, e.g., Hall and Peters, “Genetic Alterations ofCyclins, Cyclin-Dependent Kinases, and CDK Inhibitors in Human Cancer,”Adv. Cancer Res., vol. 68 (1996), pp. 67-108; and Kamb et al., “A CellCycle Regulator Potentially Involved in Genesis of Many Tumor Types,”Science, vol. 264 (1994), pp. 436-440).

Over-expression of cyclin D1 is linked to esophageal, breast, andsquamous cell carcinomas (see, e.g., DelSal et al., “Cell Cycle andCancer: Critical Events at the G.sub.1 Restriction Point,” Critical Rev.Oncogenesis, vol. 71 (1996), pp. 127-142). Genes encoding theCDK4-specific inhibitors of the p16 family frequently have deletions andmutations in familial melanoma, gliomas, leukemias, sarcomas, andpancreatic, non-small cell lung, and head and neck carcinomas (seeNobori et al., “Deletions of the Cyclin-Dependent Kinase-4 InhibitorGene in Multiple Human Cancers,” Nature, vol. 368 (1994), pp. 753-756).Amplification and/or overexpression of cyclin E has also been observedin a wide variety of solid tumors, and elevated cyclin E levels havebeen correlated with poor prognosis. In addition, the cellular levels ofthe CDK inhibitor p27, which acts as both a substrate and inhibitor ofCDK2/cyclin E, are abnormally low in breast, colon, and prostatecancers, and the expression levels of p27 are inversely correlated withthe stage of disease (see Loda et al., “Increased Proteasome-dependentDegradation of the Cyclin-Dependent Kinase Inhibitor p27 in AggressiveColorectal Carcinomas,” Nature Medicine, vol. 3 (1997), pp. 231-234).Recently there is evidence that CDK4/cyclin D might sequester p27, asreviewed in Sherr, et al., Genes Dev., Vol. 13 (1999), pp. 1501-1512.The p21 proteins also appear to transmit the p53 tumor-suppressionsignal to the CDKs; thus, the mutation of p53 in approximately 50% ofall human cancers may indirectly result in deregulation of CDK activity.

In at least one instance modulation of protein kinase activity as beenused as a treatment for an oncological condition. For example,modulation of protein kinase activity for the treatment of chronicmyeloid leukemia (CML) and gastrointestinal stroma cancers has beendemonstrated successfully with the FDA approval of Gleevec® (imatinibmesylate, produced by Novartis Pharmaceutical Corporation of EastHanover, N.J.). Gleevec is a selective Abl kinase inhibitor.

Another series of protein kinases are those that play an important roleas a checkpoint in cell cycle progression. See, e.g., Melo et al.,Current Opinion in Cell Biology 2002, 14:237-245 (2003). Proliferationof eukaryotic cells is controlled by cell cycle checkpoint pathways,which mediate progression through critical transitions of the cell cycle(reviewed by Walworth (2000), Curr. Opin. Cell Biol. 12, 697-704).Checkpoints prevent cell cycle progression at inappropriate times, suchas in response to DNA damage, and maintain the metabolic balance ofcells while the cell is arrested, and in some instances can induceapoptosis (programmed cell death) when the requirements of thecheckpoint have not been met. See, e.g., O'Connor, Cancer Surveys, 29,151-182 (1997); Nurse, Cell, 91, 865-867 (1997); Hartwell et al.,Science, 266, 1821-1828 (1994); Hartwell et al., Science, 246, 629-634(1989). Checkpoint control can occur in the G1 phase (prior to DNAsynthesis) and in G2, prior to entry into mitosis.

One series of checkpoints monitors the integrity of the genome and, uponsensing DNA damage, these “DNA damage checkpoints” block cell cycleprogression in G.sub.1 & G.sub.2 phases, and slow progression through Sphase. O'Connor, Cancer Surveys, 29, 151-182 (1997); Hartwell et al.,Science, 266, 1821-1828 (1994). This action enables DNA repair processesto complete their tasks before replication of the genome and subsequentseparation of this genetic material into new daughter cells takes place.Importantly, the most commonly mutated gene in human cancer, the p53tumor suppressor gene, produces a DNA damage checkpoint protein thatblocks cell cycle progression in G.sub.1 phase and/or induces apoptosis(programmed cell death) following DNA damage. Hartwell et al., Science,266, 1821-1828 (1994). The p53 tumor suppressor has also been shown tostrengthen the action of a DNA damage checkpoint in G.sub.2 phase of thecell cycle. See, e.g., Bunz et al., Science, 28, 1497-1501 (1998);Winters et al., Oncogene, 17, 673-684 (1998); Thompson, Oncogene, 15,3025-3035 (1997).

Given the pivotal nature of the p53 tumor suppressor pathway in humancancer, therapeutic interventions that exploit vulnerabilities inp53-defective cancer have been actively sought. One emergingvulnerability lies in the operation of the G.sub.2 checkpoint in p53defective cancer cells. Cancer cells, because they lack G.sub.1checkpoint control, are particularly vulnerable to abrogation of thelast remaining barrier protecting them from the cancer killing effectsof DNA-damaging agents: the Gsub.2 checkpoint. The G.sub.2 checkpoint isregulated by a control system that has been conserved from yeast tohumans. Important in this conserved system is a kinase, CHK1, whichtransduces signals from the DNA-damage sensory complex to inhibitactivation of the cyclin B/Cdc2 kinase, which promotes mitotic entry.See, e.g., Peng et al., Science, 277, 1501-1505 (1997); Sanchez et al.,Science, 277, 1497-1501 (1997). Inactivation of CHK1 has been shown toboth abrogate G.sub.2 arrest induced by DNA damage inflicted by eitheranticancer agents or endogenous DNA damage, as well as result inpreferential killing of the resulting checkpoint defective cells. See,e.g., Nurse, Cell, 91, 865-867 (1997); Weinert, Science, 277, 1450-1451(1997); Walworth et al., Nature, 363, 368-371 (1993); and AI-Khodairy etal., Molec. Biol. Cell., 5, 147-160 (1994).

Selective manipulation of checkpoint control in cancer cells couldafford broad utilization in cancer chemotherapeutic and radiotherapyregimens and may, in addition, offer a common hallmark of human cancer“genomic instability” to be exploited as the selective basis for thedestruction of cancer cells. A number of factors place CHK1 as a pivotaltarget in DNA-damage checkpoint control. The elucidation of inhibitorsof this and functionally related kinases such as CDS1/CHK2, a kinaserecently discovered to cooperate with CHK1 in regulating S phaseprogression (see Zeng et al., Nature, 395, 507-510 (1998); Matsuoka,Science, 282, 1893-1897 (1998)), could provide valuable new therapeuticentities for the treatment of cancer.

Another group of kinases are the tyrosine kinases. Tyrosine kinases canbe of the receptor type (having extracellular, transmembrane andintracellular domains) or the non-receptor type (being whollyintracellular). At least one of the non-receptor protein tyrosinekinases, namely, LCK is believed to mediate the transduction in T-cellsof a signal from the interaction of a cell-surface protein (Cd4) with across-linked anti-Cd4 antibody. A more detailed discussion ofnon-receptor tyrosine kinases is provided in Bolen, Oncogene, 8,2025-2031 (1993), which is incorporated herein by reference.

Receptor-type tyrosine kinases are comprised of a large number oftransmembrane receptors with diverse biological activity. In fact, about20 different subfamilies of receptor-type tyrosine kinases have beenidentified. One tyrosine kinase subfamily, designated the HER subfamily,is comprised of EGFR (HER1), HER2, HER3, and BER4. Ligands of thissubfamily of receptors identified so far include epithelial growthfactor, TGF-alpha, amphiregulin, HB-EGF, betacellulin and heregulin.Another subfamily of these receptor-type tyrosine kinases is the insulinsubfamily, which includes INS-R, IGF-R, and IR-R. The PDGF subfamilyincludes the PDGF-alpha and beta receptors, CSFIR, c-kit and FLK-II.Then there is the FLK family, which is comprised of the kinase insertdomain receptor (KDR), fetal liver kinase-1 (FLK-1), fetal liverkinase-4 (FLK-4) and the fms-like tyrosine kinase-1 (flt-1). The PDGFand FLK families are usually considered together due to the similaritiesof the two groups. For a detailed discussion of the receptor-typetyrosine kinases, see Plowman et al., DN&P 7(6): 334-339, 1994, which ishereby incorporated by reference.

The non-receptor type of tyrosine kinases is also comprised of numeroussubfamilies, including Src, Frk, Btk, Csk, Abl, Zap70, Fes/Fps, Fak,Jak, Ack, and LIMK. Each of these subfamilies is further sub-dividedinto varying receptors. For example, the Src subfamily is one of thelargest and includes Src, Yes, Fyn, Lyn, Lck, Blk, Hck, Fgr, and Yrk.The Src subfamily of enzymes has been linked to oncogenesis. For a moredetailed discussion of the non-receptor type of tyrosine kinases, seeBolen, Oncogene, 8:2025-2031 (1993), which is hereby incorporated byreference.

In addition to its role in cell-cycle control, protein kinases also playa crucial role in angiogenesis, which is the mechanism by which newcapillaries are formed from existing vessels. When required, thevascular system has the potential to generate new capillary networks inorder to maintain the proper functioning of tissues and organs. In theadult, however, angiogenesis is fairly limited, occurring only in theprocess of wound healing and neovascularization of the endometriumduring menstruation. See Merenmies, J., Parada, L. F., Henkemeyer, M.,Cell Growth & Differentiation, 8, 3-10 (1997). On the other hand,unwanted angiogenesis is a hallmark of several diseases, such asretinopathies, psoriasis, rheumatoid arthritis, age-related maculardegeneneration, and cancer (solid tumors). Folkman, Nature Med., 1,27-31 (1995). Protein kinases which have been shown to be involved inthe angiogenic process include three members of the growth factorreceptor tyrosine kinase family: VEGF-R2 (vascular endothelial growthfactor receptor 2, also know as KDR (kinase insert domain receptor) andas FLK-1); FGF-R (fibroblast growth factor receptor); and TEK (alsoknown as Tie-2).

VEGF-R2, which is expressed only on endothelial cells, binds the potentangiogenic growth factor VEGF and mediates the subsequent signaltransduction through activation of its intracellular kinase activity.Thus, it is expected that direct inhibition of the kinase activity ofVEGF-R2 will result in the reduction of angiogenesis even in thepresence of exogenous VEGF (see Strawn et al., Cancer Research, 56,3540-3545 (1996)), as has been shown with mutants of VEGF-R2 which failto mediate signal transduction. Millauer et al., Cancer Research, 56,1615-1620 (1996). Furthermore, VEGF-R2 apppears to have no function inthe adult beyond that of mediating the angiogenic activity of VEGF.Therefore, a selective inhibitor of the kinase activity of VEGF-R2 wouldbe expected to exhibit little toxicity.

Similarly, FGF-R binds the angiogenic growth factors aFGF and bFGF andmediates subsequent intracellular signal transduction. Recently, it hasbeen suggested that growth factors such as bFGF may play a critical rolein inducing angiogenesis in solid tumors that have reached a certainsize. Yoshiji et al., Cancer Research, 57, 3924-3928 (1997). UnlikeVEGF-R2, however, FGF-R is expressed in a number of different cell typesthroughout the body and may or may not play important roles in othernormal physiological processes in the adult. Nonetheless, systemicadministration of a small molecule inhibitor of the kinase activity ofFGF-R has been reported to block bFGF-induced angiogensis in micewithout apparent toxicity. Mohammad et al., EMBO Journal, 17,5996-5904(1998).

TEK (also known as Tie-2) is another receptor tyrosine kinase expressedonly on endothelial cells which has been shown to play a role inangiogenesis. The binding of the factor angiopoietin-1 results inautophosphorylation of the kinase domain of TEK and results in a signaltransduction process which appears to mediate the interaction ofendothelial cells with peri-endothelial support cells, therebyfacilitating the maturation of newly formed blood vessels. The factorangiopoietin-2, on the other hand, appears to antagonize the action ofangiopoietin-1 on TEK and disrupts angiogenesis. Maisonpierre et al.,Science, 277, 55-60 (1997).

As a result of the above-described developments, it has been proposed totreat angiogenesis by the use of compounds inhibiting the kinaseactivity of VEGF-R2, FGF-R, and/or TEK. For example, WIPO InternationalPublication No. WO 97/34876 discloses certain cinnoline derivatives thatare inhibitors of VEGF-R2, which may be used for the treatment ofdisease states associated with abnormal angiogenesis and/or increasedvascular permeability such as cancer, diabetes, psoriasis, rheumatoidarthritis, Kaposi's sarcoma, haemangioma, acute and chronicnephropathies, atheroma, arterial restinosis, autoimmune diseases, acuteinflammation and ocular diseases with retinal vessel proliferation.

In addition to the protein kinases identified above, many other proteinkinases have been considered to be therapeutic targets, and numerouspublications disclose inhibitors of kinase activity, as reviewed in thefollowing: McMahon et al., Oncologist, 5, 3-10 (2000); Garcia-Echeverriaet al., Med. Res. Rev., 20, 28-57 (2000); Holash et al., Oncogene, 18,5356-5362. (1999); Stover et al., Curr. Opin. Drug Disc. Dev., 2,274-285 (1999); Toledo et al., Curr Med. Chem., 6, 775-805 (1999);Thomas et al., J. Biol. Chem., 274, 36684-36692 (1992); Cohen, Curr. Op.Chem. Biol., 10, 544-549 (1999); Adams et al., Curr. Opin. Drug Disc.Dev., 2, 96-109 (1999); McMahon et al., Curr. Opin. Drug Disc. Dev., 1,131-146 (1998); and Strawn et al., Exp. Opin. Invest. Drugs, 7, 553-573(1998).

It can be understood, therefore, that there is a need, for effectiveinhibitors of protein kinases in order to treat or prevent diseasestates associated with abnormal cell proliferation. Moreover, as wouldbe understood by those skilled in the art, it is desirable for kinaseinhibitors to possess both high affinity for the target kinase as wellas high selectivity versus other protein kinases. Small-moleculecompounds that may be readily synthesized and are potent inhibitors ofcell proliferation are those, for example, that are inhibitors of one ormore protein kinases, such as CHK1, CHK2, VEGF, CDKs or CDK/cyclincomplexes and both receptor and non-receptor tyrosine kinases.

SUMMARY OF THE INVENTION

Based on the aforementioned evidence, we contemplated that highlyspecific inhibitors of protein kinase, such as Chk1 kinase, will have asynergistic cytotoxic effect with DNA damaging agents in many kinds oftumor cells, whilst not causing excessive toxicity in non-tumor cells.Thus, one aspect of the invention is selective protein kinasemodulators, particularly inhibitors like Chk1. Methods of the inventioninclude both use of such compounds in a synergistic fashion as mention,and also as single agents for cancer therapy.

We have unexpectedly found that analogs of3-amino-pyrazine-2-carboxamide and related compounds effectively inhibitprotein kinases such as Chk1 kinase. The compounds disclosed herein areuseful for inhibiting the protein kinase and, therefore, useful forstudying the role of protein kinase in various biological pathways aswell as to augment the efficacy of cancer therapeutics, including DNAdamaging agents. Accordingly, the invention also comprisespharmaceutical compositions comprising the compounds of the invention,as well as methods of using compounds of the invention to inhibitprotein kinase and thereby modulate kinase dependent diseases orconditions.

In another aspect, the invention provides methods of screening formodulators of kinase activity. The methods comprise combining acomposition of the invention, a kinase, and at least one candidate agentand determining the effect of the candidate agent on the kinaseactivity.

In yet another aspect, the invention also provides pharmaceutical kitscomprising one or more containers filled with one or more of theingredients of pharmaceutical compounds and/or compositions of thepresent invention, including, one or more kinase enzyme activitymodulators as described herein. Such kits can also include, for example,other compounds and/or compositions (e.g., diluents, permeationenhancers, lubricants, and the like), a device(s) for administering thecompounds and/or compositions, and written instructions in a formprescribed by a governmental agency regulating the manufacture, use orsale of pharmaceuticals or biological products, which instructions canalso reflects approval by the agency of manufacture, use or sale forhuman administration.

In still yet another aspect, the invention also provides a diagnosticagent comprising a compound of the invention and, optionally,pharmaceutically acceptable adjuvants and excipients.

These and other features and advantages of the present invention will bedescribed in more detail below.

DETAILED DESCRIPTION OF THE INVENTION

The compounds set forth in the detailed description are useful aspharmaceuticals in mammals, especially humans, for modulating proteinkinase enzymatic activity for modulating cellular activities such asuncontrolled, abnormal, or unwanted proliferation, differentiation,programmed cell death, migration and chemoinvasion. It is appreciated,however, that in some cases the cells may not be in a hyper orhypo-proliferative and/or migratory state (abnormal state) and stillrequire treatment. For example, during wound healing, the cells may beproliferating “normally,” but proliferation and migration enhancementmay be desired. Alternatively, reduction in “normal” cell proliferationand/or migration rate may be desired. Furthermore, such compounds may beused to prevent de-differentiation of post-mitotic tissue and/or cells.

Diseases or disorders associated with uncontrolled, abnormal, and/orunwanted cellular activities, especially cellular proliferation include,but are not limited to the conditions set forth in the background and tothe following:

a variety of cancers, including, but not limited to carcinoma,hematopoietic tumors of lymphoid lineage, hematopoietic tumors ofmyeloid lineage, tumors of mesenchymal origin, tumors of the central andperipheral nervous system ad other tumors including melanoma, seminomaand Kaposi's sarcoma and the like, and those further discussed below;

a disease process which features abnormal cellular proliferation, e.g.,benign prostatic hyperplasia, familial adenomatosis polyposis,neuro-fibromatosis, pulmonary fibrosis, hypertrophic scar formation,transplantation rejection, nodosum, endotoxic shock, and a variety ofcardiovascular indications, including, but not limited toatherosclerosis, dysregulated vascularization including ischemiccoronary artery disease, myocardioinfarction, ischemia, pulmonaryhypertension, stroke, emphysema, anemia, and restenosis followingangioplasty or vascular surgery;

an immune and/or inflammatory disorder, especially those involvingimmunological defects associated with aberrant B & T cell development.Such disorders can include, but are not limited to, acquiredimmunodeficiency syndrome (AIDS), Addison's disease, adult respiratorydistress syndrome, allergies, ankylosing spondylitis, amyloidosis,asthma, autoimmune hemolytic anemia, autoimmune thyroiditis, Crohn'sdisease, episodic lymphopenia with lymphocytotoxins, erythroblastosisfetalis, Goodpasture's syndrome, Graves' disease, Hashimoto'sthyroiditis, hypereosinophilia, irritable bowel syndrome and otherinterbowel diseases, Lupus, myasthenia gravis, myocardial or pericardialinflammation, pancreatitis, polymyositis, psoriasis, Reiter's syndrome,scleroderma, systemic analphylaxis, lucerative colitis, nephritis(including glomerulonephritis), gout, arthritis (such as rheumatoidarthritis and osteoarthritis), erythema, dermatitis, dermatomyositis,bronchitis, cholecystitis, and gastritis;

a disorder of carbohydrate metabolism, including but not limited todiabetic (including diabetes mellitus, diabetic retinopathy);

a parasitic, fungal and/or viral infection, including but not limited toherpes virus, poxvirus, Epstein-Barr virus, Sindbis virus andadenovirus, HIV, human papilloma virus; and

a neurodegenerative disorder, including but not limited to, Alzheimer'sdisease, amyotrophic lateral sclerosis, retinitis pignientosa,Parkinson's disease, AIDS-related dementia, spinal muscular atrophy andcerebellar degeneration, myelodysplastic syndromes, degenerativediseases of the musculoskeletal system (including but not limited toosteroporosis), cystic fibrosis, macular degeneration, and multiplesclerosis.

The present invention comprises compounds for modulating protein kinaseactivity, more particularly Checkpoint kinase activity, even moreparticularly Chk1 and Chk2, even still more particularly Chk1, ofFormula I,

or a pharmaceutically acceptable salt, hydrate, or prodrug thereof,wherein,

R¹ is independently selected from —H, halogen, —CN, —NH₂, —CF₃, —NO₂,—OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴, —C(O)N(R⁴)R⁵,—N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴, optionally substitutedlower alkyl, optionally substituted aryl, optionally substituted lowerarylalkyl, optionally substituted heterocyclyl, and optionallysubstituted lower heterocyclylalkyl;

R² and R³ are each independently selected from —H, optionallysubstituted alkyl, optionally substituted aryl, optionally substitutedlower arylalkyl, optionally substituted heterocyclyl, and optionallysubstituted lower heterocyclylalkyl; or

R² and R³, together with the nitrogen to which they are attached, arecombined to form an optionally substituted five- to seven-memberedheterocyclyl, said five- to seven-membered heterocyclyl optionallycontaining at least one additional heteroatom selected from N, O, S, andP;

R⁴ is —H or R⁵;

R⁵ is selected from optionally substituted lower alkyl, optionallysubstituted aryl, optionally substituted lower arylalkyl, optionallysubstituted heterocyclyl, and optionally substituted lowerheterocyclylalkyl; or

R⁴ and R⁵, when taken together with a common nitrogen to which they areattached, form an optionally substituted five- to seven-memberedheterocyclyl, said optionally substituted five- to seven-memberedheterocyclyl optionally containing at least one additional heteroatomselected from N, O, S, and P;

Z is —N═ or —C(H)═;

A is selected from —C(═O)—, —C(═S)—, —C(═NR⁶)—, and —R⁷, when A is —R⁷,E does not exist;

R⁶ is selected from —H, —NO₂, —N(R²)R³, —NC(═NR²)N(R²)R³, —CN, —OR⁴,optionally substituted lower alkyl, optionally substitutedheteroalicyclylalkyl, optionally substituted aryl, optionallysubstituted arylalkyl and optionally substituted heteroalicyclic;

R⁷ is optionally substituted five- to seven-membered heterocyclyl, saidfive- to seven-membered heterocyclyl optionally containing at least oneadditional heteroatom selected from N, O, S, and P;

E is selected from —N(R⁸)R⁹—, —NN(R²)R³—, —NNC(═O)N(R²)R³—, —OR⁴, and—R¹⁰;

R⁸ is —H or optionally substituted alkyl;

R⁹ is selected from —H, optionally substituted heteroalicyclylalkyl,optionally substituted heteroarylalkyl, and optionally substitutedheteroalicyclic; or

R⁸ and R⁹, together with the nitrogen to which they are attached, arecombined to form an optionally substituted five- to seven-memberedheteroalicyclyl, said five- to seven-membered heteroalicyclyl optionallycontaining at least one additional heteroatom selected from N, O, S, andP;

R¹⁰ is selected from —H, optionally substituted heteroalicyclylalkyl,optionally substituted heteroalicyclic, optionally substitutedarylalkyl, optionally substituted aryl, and optionally substitutedalkyl;

W is either an optionally substituted six- to ten-membered arylene or anoptionally substituted five- to ten-membered heteroarylene;

-   -   X is selected from a single bond, —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₀₋₃—,        —(CH₂)₀₋₃CO₂(CH₂)₀₋₃—, —(CH₂)₀₋₃SO₂N(R⁴)(CH₂)₀₋₃—,        —N(R⁴)(CH₂)₂₋₃O—, —(CH₂)₀₋₃N(R⁴)C(═O)N(R⁴)(CH₂)₀₋₂—,        —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃O—, —(CH₂)₀₋₃S(O)₀₋₂(CH₂)₀₋₃—,        —N(R⁴)(CH₂)₂₋₃N(R⁴)—, —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₁₋₃C(═O)—,        —(CH₂)₀₋₃OC(═O)N(R⁴)(CH₂)₀₋₃—, —C(═O)N(R⁴)N(R⁴)—,        —(CH₂)₀₋₃CO₂(CH₂)₂₋₃N(R⁴—, —(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃O—,        —(CH₂)₀₋₃N(R⁴)(CH₂)₀₋₃—, —C(═O)N(R⁴)(CH₂)₂₋₃N(R⁴)—,        —O(CH₂)₂₋₃O—, —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃S(O)₀₋₂—,        —(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃S(O)₀₋₂—, —(CH₂)₀₋₃O(CH₂)₀₋₃—,        optionally substituted alkoxyl, and optionally substituted lower        alkylene, wherein any —CH₂— in X is optionally substituted; and

Y is selected from —H, optionally substituted lower alkyl, optionallysubstituted aryl, and optionally substituted heterocyclyl;

-   -   provided the compound is not:

wherein R²³, R²⁴, and R²⁵ are —H; and R²⁶ is —H, —Cl, —CH₃, or —OCH₃; or

wherein R²³ is —C(NH)NH₂; R²⁴ is —CH₃; R²⁵ is H; and R²⁶ is —Cl; or

wherein R²³ is —H, methyl, ethyl, propyl, isopropyl, butyl, t-butyl,1-methylpropyl, hydroxyethyl; and R²⁴, R²⁵, and R²⁶ are H; or

wherein R²³ is —H; R²⁴ is butyl; and R²⁵ and R²⁶ are methoxy; or

wherein R²³ 1-methylpropyl; R²⁴ is —CHO; R²⁵ is —H; and R²⁶ is —Cl; or

wherein R²³ is —H; R²⁴ is —CH₃; and R²⁵ and R²⁶ are —H.

In one example, the compound is according to paragraph [0039], wherein Zis ═N—.

In another example, the compound is according to paragraph [0040],wherein R¹ is —H.

In another example, the compound is according to paragraph [0041];wherein R² is —H and R³ is either —H or lower alkyl.

In another example, the compound is according to paragraph [0042],wherein R² and R³ are —H.

In another example, the compound is according to paragraph [0043],wherein A is R⁷, and R⁷ is either

wherein each G¹ is independently ═N— or ═C(R¹¹)—, L is selected from—O—, —S(O)₀₋₂—, and —NR¹¹, wherein each R¹¹ is independently selectedfrom —H, halogen, —CN, —NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵,—SO₂N(R⁴)R⁵, —CO₂R⁴, —C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵,—N(R⁴)CO₂R⁵, —C(O)R⁴, optionally substituted lower alkyl, optionallysubstituted aryl, optionally substituted lower arylalkyl, optionallysubstituted heterocyclyl, and optionally substituted lowerheterocyclylalkyl; or optionally two R¹¹'s form a ring system fused withthe existing ring of R⁷, said ring system substituted with 0 to 3additional of R¹¹ and said ring system optionally containing between 1and 3 heteroatoms.

In another example, the compound is according to paragraph [0044],wherein R⁷ is selected from

wherein R^(11a) is selected from —H, lower alkyl, and —NR⁴R⁵; andR^(11b) is selected from optionally substituted alkyl, optionallysubstituted aryl, optionally substituted arylalkyl, optionallysubstituted heteroaryl, optionally substituted heteroarylalkyl, andoptionally substituted heteroalicyclic; and L is selected from —O—,—S(O)₀₋₂—.

In another example, the compound is according to paragraph [0045],wherein R^(11b) is selected from optionally substituted alkyl,

wherein each R¹² is independently selected from —H, halogen, oxo, —CN,—NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(r⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴,optionally substituted lower alkyl, optionally substituted aryl,optionally substituted lower arylalkyl, optionally substitutedheterocyclyl, and optionally substituted lower heterocyclylalkyl; R¹³ isselected from —H, lower alkyl, and acyl; Q is either ═N— or ═C(R¹²)—;and M is selected from —O—, —S(O)₀₋₂—, and —NR¹³.

In another example, the compound is according to paragraph [0046],wherein W is

wherein each G² is independently ═N— or ═C(R¹⁴)—, wherein each R¹⁴ isindependently selected from —H, halogen, —CN, —NH₂, —CF₃, —NO₂, —OR⁴,—N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴, —C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵,—N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴, optionally substituted lower alkyl,optionally substituted aryl, optionally substituted lower arylalkyl,optionally substituted heterocyclyl, and optionally substituted lowerheterocyclylalkyl.

In another example, the compound is according to paragraph [0047],wherein W is

In another example, the compound is according to paragraph [0048],wherein X is selected from —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₀₋₃—,—(CH₂)₀₋₃SO₂N(R⁴)(CH₂)₀₋₃—, —N(R⁴)(CH₂)₂₋₃O,—(CH₂)₀₋₃N(R⁴)C(═O)N(R⁴)(CH₂)₀₋₃—, —C(═O)N(R⁴)N(R⁴)—,—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃O—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—(CH₂)₀₋₃N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₁₋₃C(═O)—,—O(CH₂)₂₋₃O—, —(CH₂)₀₋₃OC(═O)N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃O(CH₂)₀₋₃—,—(CH₂)₀₋₃CO₂(CH₂)₂₋₃N(R⁴)—, —CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃O—,—C(═O)N(R⁴)(CH₂)₂₋₃N(R⁴)—, optionally substituted alkoxyl, andoptionally substituted lower alkylene.

In another example, the compound is according to paragraph [0049],wherein X is selected from —C(═O)N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂C(═O)N(H)—,—C(═O)N(H)—, —SO₂N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂SO₂N(H)—, —SO₂N(H)—,—N(H)C(═O)N(H)(CH₂)₁₋₂—, —N(H)C(═O)N(H)—, —(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—,—(CH₂)₀₋₂O(CH₂)₀₋₂, —C(═O)N(H)N(H)—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—OCH₂C(═O)N(H)CH₂—, —(CH₂)₁₋₂N(H)C(═O)N(H)—, —OCH₂CH₂O—,—N(R⁴)CH₂C(═O)N(H)CH₂—, —(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—, optionallysubstituted alkoxyl, and optionally substituted lower alkylene.

In another example, the compound is according to paragraph [0050],wherein Y is selected from optionally substituted cycloalkyl, optionallysubstituted phenyl, and optionally substituted five- to six-memberedheterocyclyl.

In another example, the compound is according to paragraph [0051],wherein Y is selected from Table 1.

TABLE 1

wherein each R¹⁵ is independently selected from —H, halogen, oxo, —CN,—NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴,optionally substituted lower alkyl, optionally substituted aryl,optionally substituted lower arylalkyl, optionally substitutedheterocyclyl, and optionally substituted lower heterocyclylalkyl.

In another example, the compound is according to paragraph [0052],wherein R^(11b) is selected from optionally substituted alkyl,optionally substituted phenyl, optionally substituted pyridyl, andoptionally substituted heteroalicyclic.

In another example, the compound is according to paragraph [0053],wherein R⁷ is

In another example, the compound is according to paragraph [0054],wherein R^(11b) is selected from optionally substituted morpholine,optionally substituted pyrrolidine, optionally substituted piperidine,and optionally substituted azepane.

In another example, the compound is according to paragraph [0055],wherein R^(11b)

where R¹⁴ is either —H or lower alkyl.

In another example, the compound is according to paragraph [0054],wherein R^(11b) is a pyridine.

In another example, the compound is according to paragraph [0057],wherein R^(11b) is a pyridine bearing a 2-amino group.

In another example, the compound is according to paragraph [0042],wherein A is —C(═O)— or —C(═NR⁶)—.

In another example, the compound is according to paragraph [0059],wherein A is —C(═O)—.

In another example, the compound is according to paragraph [0060],wherein E is selected from Table 2.

TABLE 2

wherein each R¹⁶ is independently selected from —H, optionallysubstituted lower alkyl, —CO₂R⁴, and —C(═O)R⁴; or optionally two of R¹⁶,together with the nitrogen or nitrogens to which they are attached, forna heterocyclic ring; each R¹⁷ is independently selected from —H,halogen, oxo, —CN, —NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵,—SO₂N(R⁴)R⁵, —CO₂R⁴, —C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵,—N(R⁴)CO₂R⁵, —(O)R⁴, optionally substituted lower alkyl, optionallysubstituted aryl, optionally substituted lower arylalkyl, optionallysubstituted heterocyclyl, and optionally substituted lowerheterocyclylalkyl; R¹⁸ is optionally substituted lower alkyl; J¹ is asaturated bridged ring system containing at least one nitrogen ringatom, said saturated bridged ring system having a geometry selected fromthe group consisting of [4.4.0], [4.3.0], [4.2.0], [4.1.0], [3.3.0],[3.2.0], and [3.1.0]; and J² is a saturated bridged ring systemcontaining at least one nitrogen ring atom, said saturated bridged ringsystem having a geometry selected from the group consisting of [4.4.0],[4.3.0], [4.2.0], [4.1.0], [3.3.0], [3.2.0], and [3.1.0], wherein thenitrogen bearing R¹⁶ and any nitrogen in J² must have at least twocarbons between them.

In another example, the compound is according to paragraph [0061],wherein W is

wherein each G² is independently ═N— or ═C(R¹⁴)—, wherein each R¹⁴ isindependently selected from —H, halogen, —CN, —NH₂, —CF₃, —NO₂, —OR⁴,—N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴, —C(O)N(R⁴)R⁵, —N(⁴)SO₂R⁵,—N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴, optionally substituted lower alkyl,optionally substituted aryl, optionally substituted lower arylalkyl,optionally substituted heterocyclyl, and optionally substituted lowerheterocyclylalkyl.

In another example, the compound is according to paragraph [0062],wherein W is

In another example, the compound is according to paragraph [0063],wherein X is selected from —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₀₋₃—,—(CH₂)₀₋₃SO₂N(R⁴)(CH₂)₀₋₃—, —N(R⁴)(CH₂)₂₋₃O,—(CH₂)₀₋₃N(R⁴)C(═O)N(R⁴)(CH₂)₀₋₃—, —C(═O)N(R⁴)N(R⁴)—,—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃O—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—(CH₂)₀₋₃N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₁₋₃C(═O)—,—O(CH₂)₂₋₃O—, —(CH₂)₀₋₃OC(═O)N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃O(CH₂)₀₋₃—,—(CH₂)₀₋₃CO₂(CH₂)₂₋₃N(R⁴)—, —(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃O—,—C(═O)N(R⁴)(CH₂)₂₋₃N(R⁴)—, optionally substituted alkoxyl, andoptionally substituted lower alkylene.

In another example, the compound is according to paragraph [0064],wherein X is selected from —C(═O)N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂C(═O)N(H)—,—C(═O)N(H)—, —SO₂N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂SO₂N(H)—, —SO₂N(H)—,—N(H)C(═O)N(H)(CH₂)₁₋₂—, —N(H)C(═O)N(H)—, —(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—,—(CH₂)₀₋₂O(CH₂)₀₋₂, —C(═O)N(H)N(H)—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—OCH₂C(═O)N(H)CH₂—, —(CH₂)₁₋₂N(H)C(═O)N(H)—, —OCH₂CH₂O—,—N(R⁴)CH₂C(═O)N(H)CH₂—, —(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—, optionallysubstituted alkoxyl, and optionally substituted lower alkylene.

In another example, the compound is according to paragraph [0065],wherein Y is selected from optionally substituted cycloalkyl, optionallysubstituted phenyl, and optionally substituted five- to six-memberedheterocyclyl.

In another example, the compound is according to paragraph [0066],wherein Y is selected from Table 3.

TABLE 3

wherein each R¹⁵ is independently selected from —H, halogen, oxo, —CN,—NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴,optionally substituted lower alkyl, optionally substituted aryl,optionally substituted lower arylalkyl, optionally substitutedheterocyclyl, and optionally substituted lower heterocyclylalkyl.

In another example, the compound is according to paragraph [0067],wherein E is either

In another example, the compound is according to paragraph [0068],wherein E is either

In another example, the compound is according to paragraph [0069],wherein R² and R³ are —H.

In another example, the compound is according to paragraph [0070],wherein A is —C(═NR⁶)—.

In another example, the compound is according to paragraph [0071],wherein E is selected from —H, lower alkyl, and a group listed in Table4,

TABLE 4

R⁶ is selected from —H, —OH, lower alkyl, —NO₂, —CN, lower alkoxy, and agroup listed in Table 5,

TABLE 5

wherein each R¹⁹ is independently either —H or lower alkyl;

each R²⁰ is independently selected from —H, halogen, oxo, —CN, —NH₂,—CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴,optionally substituted lower alkyl, optionally substituted aryl,optionally substituted lower arylalkyl, optionally substitutedheterocyclyl, and optionally substituted lower heterocyclylalkyl;

and R²¹ is selected from —H, —OH, lower alkyl, —NO₂, —CN, lower alkoxy.

In another example, the compound is according to paragraph [0072],wherein W is

In another example, the compound is according to paragraph [0073],wherein X is selected from —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₀₋₃—,—(CH₂)₀₋₃SO₂N(R⁴)(CH₂)₀₋₃—, —N(R⁴)(CH₂)₂₋₃O,—(CH₂)₀₋₃N(R⁴)C(═O)N(R⁴)(CH₂)₀₋₃—, —C(═O)N(R⁴)N(R⁴)—,—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃O—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—(CH₂)₀₋₃N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₁₋₃C(═O)—,—O(CH₂)₂₋₃O—, —(CH₂)₀₋₃OC(═O)N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃O(CH₂)₀₋₃—,—(CH₂)₀₋₃CO₂(CH₂)₂₋₃N(R⁴)—, —(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃O—,—C(═O)N(R⁴)(CH₂)₂₋₃N(R⁴)—, optionally substituted alkoxyl, andoptionally substituted lower alkylene.

In another example, the compound is according to paragraph [0074],wherein X is selected from —C(═O)N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂C(═O)N(H)—,—C(═O)N(H)—, —SO₂N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂SO₂N(H)—, —SO₂N(H)—,—N(H)C(═O)N(H)(CH₂)₁₋₂—, —N(H)C(═O)N(H)—, —(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—,—(CH₂)₀₋₂O(CH₂)₀₋₂, —C(═O)N(H)N(H)—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—OCH₂C(═O)N(H)CH₂—, —(CH₂)₁₋₂N(H)C(═O)N(H)—, —OCH₂CH₂O—,—N(R⁴)CH₂C(═O)N(H)CH₂—, —(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—, optionallysubstituted alkoxyl, and optionally substituted lower alkylene.

In another example, the compound is according to paragraph [0075],wherein Y is selected from optionally substituted cycloalkyl, optionallysubstituted phenyl, and optionally substituted five- to six-memberedheterocyclyl.

In another example, the compound is according to paragraph [0076],wherein Y is selected from Table 6.

TABLE 6

wherein each R¹⁵ is independently selected from —H, halogen, oxo, —CN,—NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴,optionally substituted lower alkyl, optionally substituted aryl,optionally substituted lower arylalkyl, optionally substitutedheterocyclyl, and optionally substituted lower heterocyclylalkyl.

In another example, the compound is according to paragraph [0039], offormula II,

wherein E is selected from Table 7,

TABLE 7

wherein each R¹⁶ is independently selected from —H, optionallysubstituted lower alkyl, —CO₂R⁴, and —C(═O)R⁴,

or optionally two of R¹⁶, together with the nitrogen or nitrogens towhich they are attached, form a heterocyclic ring;

each R¹⁷ is independently selected from —H, halogen, oxo, —CN, —NH₂,—CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, optionally substituted lowerarylalkyl, optionally substituted heterocyclyl, and optionallysubstituted lower heterocyclylalkyl;

R¹⁸ is optionally substituted lower alkyl;

J¹ is a saturated bridged ring system containing at least one nitrogenring atom, said saturated bridged ring system having a geometry selectedfrom the group consisting of [4.4.0], [4.3.0], [4.2.0], [4.1.0],[3.3.0], [3.2.0], and [3.1.0];

J² is a saturated bridged ring system containing at least one nitrogenring atom, said saturated bridged ring system having a geometry selectedfrom the group consisting of [4.4.0], [4.3.0], [4.2.0], [4.1.0],[3.3.0], [3.2.0], and [3.1.0], wherein the nitrogen bearing R¹⁶ and anynitrogen in J² must have at least two carbons between them.

X is selected from —C(═O)N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂C(═O)N(H)—,—C(═O)N(H)—, —SO₂N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂SO₂N(H)—, —SO₂N(H)—,—N(H)C(═O)N(H)(CH₂)₁₋₂—, —N(H)C(═O)N(H)—, —(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—,—(CH₂)₀₋₂O(CH₂)₀₋₂, —C(═O)N(H)N(H)—, —(R⁴)(CH₂)₂₋₃N(R⁴)—,—OCH₂C(═O)N(H)CH₂—, —(CH₂)₁₋₂N(H)C(═O)N(H)—, —OCH₂CH₂O,—N(R⁴)CH₂C(═O)N(H)CH₂—, —(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—, optionallysubstituted alkoxyl, and optionally substituted lower alkylene;

Y is selected from Table 8,

TABLE 8

wherein each R¹⁵ is independently selected from —H, halogen, oxo, —CN,—NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴,optionally substituted lower alkyl, optionally substituted aryl,optionally substituted lower arylalkyl, optionally substitutedheterocyclyl, and optionally substituted lower heterocyclylalkyl; and,

each R²² is independently selected from —H, halogen, —CN, —NH₂, —CF₃,—NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴, —C(O)N(R⁴)R⁵,—N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴, optionailly substitutedlower alkyl, optionally substituted aryl, optionally substituted lowerarylalkyl, optionally substituted heterocyclyl, and optionallysubstituted lower heterocyclylalkyl.

In another example, the compound is according to paragraph [0039], offormula

wherein, each G is independently ═N— or ═C(R¹¹)—;

L is selected from —O—, —S(O)₀₋₂—, and —NR¹¹; each R¹¹ is independentlyselected from —H, halogen, —CN, —NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵,—S(O)₀₋₂R⁵, —SO₂N(⁴)R⁵, —CO₂R⁴, —C(O)N(⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵,—N(R⁴)CO₂R⁵, —C(O)R⁴, optionally substituted lower alkyl, optionallysubstituted aryl, optionally substituted lower arylalkyl, optionallysubstituted heterocyclyl, and optionally substituted lowerheterocyclylalkyl; or

optionally two R¹¹'s form a ring system fused with the existing ring ofR⁷, said ring system substituted with 0 to 3 additional of R¹¹ and saidring system optionally containing between 1 and 3 heteroatoms;

X is selected from —C(═O)N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂C(═O)N(H)—,—C(═O)N(H)—, —SO₂N(R)(CH₂)₁₋₂—, —(CH₂)₁₋₂SO₂N(H)—, —SO₂N(H)—,—N(H)C(═O)N(H)(CH₂)₁₋₂—, —N(H)C(═O)N(H)—, —(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—,—(CH₂)₀₋₂O(CH₂)₀₋₂, —C(═O)N(H)N(H)—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—OCH₂C(═O)N(H)CH₂—, —(CH₂)₁₋₂N(H)C(═O)N(H)—, —OCH₂CH₂O,—N(R⁴)CH₂C(═O)N(H)CH₂—, —(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—, optionallysubstituted alkoxyl, and optionally substituted lower alkylene;

Y is selected from Table 9,

TABLE 9

wherein each R¹⁵ is independently selected from —H, halogen, oxo, —CN,—NH₂, —CF₃, —NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴,—C(O)N(R⁴)R⁵, —N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴,optionally substituted lower alkyl, optionally substituted aryl,optionally substituted lower arylalkyl, optionally substitutedheterocyclyl, and optionally substituted lower heterocyclylalkyl; and,

each R²² is independently selected from —H, halogen, —CN, —NH₂, —CF₃,—NO₂, —OR⁴, —N(R⁴)R⁵, —S(O)₀₋₂R⁵, —SO₂N(R⁴)R⁵, —CO₂R⁴, —C(O)N(R⁴)R⁵,—N(R⁴)SO₂R⁵, —N(R⁴)C(O)R⁵, —N(R⁴)CO₂R⁵, —C(O)R⁴, optionally substitutedlower alkyl, optionally substituted aryl, optionaaly substituted lowerarylalkyl, optionally substituted heterocyclyl, and optionallysubstituted lower heterocyclylalkyl.

In another example, the compound is according to paragraph [0039],wherein the copound is selected from Table 10.

TABLE 10 # Name 13-amino-6-phenyl-N-(2-phenylethyl)pyrazine-2-carboxamide 23-amino-6-phenyl-N-(phenylmethyl)pyrazine-2-carboxamide 33-amino-6-(3-chlorophenyl)pyrazine-2-carboxamide 43-amino-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-6-phenylpyrazine-2-carboxamide53-amino-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-6-phenylpyrazine-2-carboxamide6 3-amino-N-(2,3-dihydro-1H-inden-2-yl)-6-phenylpyrazine-2-carboxamide 73-amino-6-(2-chlorophenyl)pyrazine-2-carboxamide 83-amino-N-cyclopentyl-6-phenylpyrazine-2-carboxamide 93-amino-N,N-dimethyl-6-phenylpyrazine-2-carboxamide 103-amino-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide 115-phenyl-3-(pyrrolidin-1-ylcarbonyl)pyrazin-2-amine 123-amino-N-(cyclopropylmethyl)-6-phenylpyrazine-2-carboxamide 133-amino-6-phenyl-N-(tetrahydrofuran-2-ylmethyl)pyrazine-2-carboxamide 143-amino-N-cyclohexyl-6-phenylpyrazine-2-carboxamide 156-phenyl-N-propyl-3-(propylamino)pyrazine-2-carboxamide 163-amino-6-(2-methylphenyl)pyrazine-2-carboxamide 173-amino-6-[2-(methyloxy)phenyl]pyrazine-2-carboxamide 183-amino-6-(2,4-difluorophenyl)pyrazine-2-carboxamide 193-amino-6-(3-fluorophenyl)pyrazine-2-carboxamide 203-amino-N-cyclopropyl-6-phenylpyrazine-2-carboxamide 213-amino-6-(3,4-difluorophenyl)pyrazine-2-carboxamide 223-amino-6-(4-fluorophenyl)-N-methylpyrazine-2-carboxamide 233-amino-6-[4-(ethyloxy)phenyl]pyrazine-2-carboxamide 243-amino-6-[3-(ethyloxy)phenyl]pyrazine-2-carboxamide 253-amino-6-(1,3-benzodioxol-5-yl)pyrazine-2-carboxamide 263-amino-6-naphthalen-1-ylpyrazine-2-carboxamide 273-amino-6-naphthalen-2-ylpyrazine-2-carboxamide 283-amino-6-{3-[(trifluoromethyl)oxy]phenyl}pyrazine-2-carboxamide 293-amino-6-[3-(aminocarbonyl)phenyl]pyrazine-2-carboxamide 306-[3-(acetylamino)phenyl]-3-aminopyrazine-2-carboxamide 313-amino-6-biphenyl-4-ylpyrazine-2-carboxamide 323-amino-6-[4-(dimethylamino)phenyl]pyrazine-2-carboxamide 333-amino-6-(3-methylphenyl)pyrazine-2-carboxamide 34 methyl3-[5-amino-6-(aminocarbonyl)pyrazin-2-yl]benzoate 353-amino-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide 363-amino-6-(3-hydroxyphenyl)pyrazine-2-carboxamide 373-amino-6-(1-benzofuran-2-yl)pyrazine-2-carboxamide 383-(methylamino)-6-phenylpyrazine-2-carboxamide 396-phenyl-3-[(phenylmethyl)amino]pyrazine-2-carboxamide 406-phenyl-3-(propylamino)pyrazine-2-carboxamide 413-amino-6-biphenyl-3-ylpyrazine-2-carboxamide 423-[5-amino-6-(aminocarbonyl)pyrazin-2-yl]benzoic acid 433-amino-6-{4-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide 443-amino-N-methyl-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide45 3-amino-6-(3-hydroxyphenyl)-N-methylpyrazine-2-carboxamide 463-amino-N-[2-(methyloxy)ethyl]-6-phenylpyrazine-2-carboxamide 47N-[2-(acetylamino)ethyl]-3-amino-6-phenylpyrazine-2-carboxamide 483-amino-6-phenylpyrazine-2-carbohydrazide 493-amino-N-hydroxy-6-phenylpyrazine-2-carboxamide 503-amino-6-[3-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide 513-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide 523-amino-6-[4-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide 533-amino-N-methyl-6-(3-methylphenyl)pyrazine-2-carboxamide 543-amino-N-methyl-6-[4-(methyloxy)phenyl]pyrazine-2-carboxamide 553-amino-6-biphenyl-3-yl-N-methylpyrazine-2-carboxamide 566-[3-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide 573-amino-6-[3-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide 583-amino-6-[4-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide 593-amino-N-methyl-6-{3-[(1E)-N-methylethanimidoyl]phenyl}pyrazine-2-carboxamide 603-amino-N-methyl-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide 613-amino-6-(4-fluoro-3-methylphenyl)-N-methylpyrazine-2-carboxamide 623-amino-N-methyl-6-pyridin-3-ylpyrazine-2-carboxamide 636-[4-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide 643-amino-N-methyl-6-{3-[(methylamino)carbonyl]phenyl}pyrazine-2-carboxamide65 6-(3-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamide 663-amino-N-methyl-6-(5-pyridin-3-yl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide 673-amino-6-(5-cyclopentyl-1,2,4-oxadiazol-3-yl)-N-methylpyrazine-2-carboxamide 683-amino-6-(5-cyclohexyl-1,2,4-oxadiazol-3-yl)-N-methylpyrazine-2-carboxamide693-amino-N-methyl-6-(5-phenyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide70 3-amino-N-methyl-6-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]pyrazine-2-carboxamide 713-amino-N-methyl-6-(5-methyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide723-amino-N-methyl-6-[5-(2-phenylethyl)-1,2,4-oxadiazol-3-yl]pyrazine-2-carboxamide 733-amino-N-methyl-6-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide 743-amino-6-[5-(1,1-dimethylethyl)-1,2,4-oxadiazol-3-yl]-N-methylpyrazine-2-carboxamide 753-amino-6-(5-furan-2-yl-1,2,4-oxadiazol-3-yl)-N-methylpyrazine-2-carboxamide76 3-amino-6-[4-(dimethylamino)phenyl]-N-methylpyrazine-2-carboxamide 773-amino-N-methyl-6-{4-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide78 3-amino-6-(3,5-dimethylphenyl)-N-methylpyrazine-2-carboxamide 796-(4-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamide 803-amino-6-[3,4-bis(methyloxy)phenyl]-N-methylpyrazine-2-carboxamide 813-amino-N-methyl-6-{3-[(phenylcarbonyl)amino]phenyl}pyrazine-2-carboxamide823-amino-N-methyl-6-{3-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide83 3-amino-N-methyl-6-[3-(1H-tetrazol-5-yl)phenyl]pyrazine-2-carboxamide843-amino-N-methyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 853-amino-6-[3-(aminocarbonyl)phenyl]-N-methylpyrazine-2-carboxamide 863-amino-6-{3-[(dimethylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 873-amino-N-methyl-6-[4-(methylsulfonyl)phenyl]pyrazine-2-carboxamide 883-amino-6-(3-aminophenyl)-N-ethylpyrazine-2-carboxamide 893-amino-6-[3-({[(4-fluorophenyl)amino]carbonyl}amino)phenyl]-N-methylpyrazine-2-carboxamide 90 3-amino-N-methyl-6-{3-[({[4-(methyloxy)phenyl]amino}carbonyl)amino]phenyl}pyrazine-2-carboxamide 916,6′-[(oxomethanediyl)bis(iminobenzene-3,1-diyl)]bis(3-amino-N-methylpyrazine-2-carboxamide) 923-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid 933-amino-N-methyl-6-{3-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazine-2-carboxamide 943-amino-N-methyl-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 95 3-amino-N-methyl-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 963-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 973-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 983-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 993-amino-N-methyl-6-(3-{[methyl(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1003-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 101 3-amino-N-methyl-6-[3-({[(4-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1023-amino-N-methyl-6-{3-[({[4-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide103 3-amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1043-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 1053-amino-N-methyl-6-[3-({[3-(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 1063-amino-N-methyl-6-[3-({[4-(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 107 3-amino-N-methyl-6-{3-[({[3-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide108 3-amino-N-methyl-6-{3-[({(1R)-1-[4-(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 1093-amino-N-methyl-6-{3-[({[2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide110 3-amino-6-[3-({[(3-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1113-amino-6-(3-{[(4-chlorophenyl)carbonyl]amino}phenyl)-N-methylpyrazine-2-carboxamide 1123-amino-6-[3-({[1-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1133-amino-6-{3-[({[2,3-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 1143-amino-6-(3-{[bis(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 1153-amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 1163-amino-6-(3-{[ethyl(pyridin-4-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 1173-amino-N-methyl-6-(3-{[4-(phenylmethyl)piperazin-1-yl]carbonyl}phenyl)pyrazine-2-carboxamide 1183-amino-N-methyl-6-[3-({[1-(phenylmethyl)piperidin-4-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1193-amino-N-methyl-6-(3-{[(4-methylphenyl)carbonyl]amino}phenyl)pyrazine-2-carboxamide 120 3-amino-N-methyl-6-[3-({[(5-methylpyrazin-2-yl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1213-amino-N-methyl-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1223-amino-N-methyl-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1233-amino-N-methyl-6-(3-{[(pyridin-4-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1243-amino-6-{3-[(furan-2-ylcarbonyl)amino]phenyl}-N-methylpyrazine-2-carboxamide 1253-amino-6-[3-({[(3-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1263-amino-6-(3-{[(cyclohexylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 1273-amino-N-methyl-6-(3-{[(2-phenylpropyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1283-amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1293-amino-6-[3-({[2-(2-chlorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 130 3-amino-N-methyl-6-{3-[({2-[2-(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 1313-amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1323-amino-N-methyl-6-[3-({[2-(2-thienyl)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1333-amino-6-{3-[(cyclohexylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 134 1,1-dimethylethyl4-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)piperidine-1-carboxylate 1353-amino-N-methyl-6-(3-{[(piperidin-4-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1363-amino-N-methyl-6-[3-(5-phenyl-1,2,4-oxadiazol-3-yl)phenyl]pyrazine-2-carboxamide 1373-amino-N-methyl-6-{3-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}pyrazine-2-carboxamide 1383-amino-N-methyl-6-{3-[5-(2-phenylethyl)-1,2,4-oxadiazol-3-yl]phenyl}pyrazine-2-carboxamide 1393-amino-6-(3-{[(1,1-dimethylethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 1403-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1413-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1423-amino-N-methyl-6-{3-[(phenylamino)carbonyl]phenyl}pyrazine-2-carboxamide1433-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1443-amino-N-methyl-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1453-amino-N-methyl-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1463-amino-N-methyl-6-[3-({[(1R)-1-phenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1473-amino-N-methyl-6-[3-({[(1S)-1-phenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 148 3-amino-N-methyl-6-[3-({[(1R,2S)-2-phenylcyclopropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 149phenylmethyl 4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoate1503-amino-N-methyl-6-(4-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1513-amino-N-methyl-6-(4-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1523-amino-6-[4-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 153 3-amino-N-methyl-6-[4-({[(4-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1543-amino-6-(4-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 1553-amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide 1563-amino-N-methyl-6-[3-({[3-(phenyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 1573-amino-6-{3-[(diphenylacetyl)amino]phenyl}-N-methylpyrazine-2-carboxamide1583-amino-N-methyl-6-{3-[(phenylacetyl)amino]phenyl}pyrazine-2-carboxamide159 3-amino-N-methyl-6-{3-[(3-phenylpropanoyl)amino]phenyl}pyrazine-2-carboxamide 1603-amino-N-methyl-6-(3-{[(1R)-1,2,3,4-tetrahydronaphthalen-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 1613-amino-N-methyl-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 1623-amino-N-methyl-6-{3-[({[3,4,5-tris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide163 3-amino-N-methyl-6-{3-[({(1R,2R)-2-[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide164 3-amino-N-methyl-6-{3-[({(1S,2S)-2-[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide165 3-amino-6-(3-cyanophenyl)-N-methylpyrazine-2-carboxamide 1663-amino-6-{3-[(cyclopentylcarbonyl)amino]phenyl}-N-methylpyrazine-2-carboxamide 1673-amino-6-(3-{[(4-cyanophenyl)carbonyl]amino}phenyl)-N-methylpyrazine-2-carboxamide 168 3-amino-N-methyl-6-[3-({[(phenylmethyl)amino]carbonyl}amino)phenyl]pyrazine-2-carboxamide 1693-amino-N-methyl-6-(3-{[(naphthalen-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1703-amino-N-methyl-6-(3-{[(tetrahydrofuran-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1713-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 172 3-amino-6-{3-[({[3-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 1733-amino-6-{3-[({2-[3,5-bis(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 1743-amino-N-methyl-6-{3-[(2-phenylethyl)oxy]phenyl}pyrazine-2-carboxamide1753-amino-N-methyl-6-(3-{[2-(4-methylpiperidin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide 1763-amino-6-[3-({2-[4-(2-hydroxyethyl)piperidin-1-yl]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide 1773-amino-6-(3-{[2-(3-hydroxypyrrolidin-1-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide 1783-amino-6-[3-({2-[ethyl(phenylmethyl)amino]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide 1793-amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide 1803-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 1813-amino-N-methyl-6-(3-{[2-(4-phenylpiperazin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide 1823-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 183 3-amino-N-methyl-6-[3-({2-[methyl(phenylmethyl)amino]ethyl}oxy)phenyl]pyrazine-2-carboxamide 1843-amino-N-methyl-6-{3-[({[4-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide185 3-amino-N-methyl-6-{3-[(2-morpholin-4-ylethyl)oxy]phenyl}pyrazine-2-carboxamide 1863-amino-6-[3-({2-[(cyclopropylmethyl)(propyl)amino]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide 1873-amino-N-methyl-6-[3-({2-[4-(phenylmethyl)piperidin-1-yl]ethyl}oxy)phenyl]pyrazine-2-carboxamide 1883-amino-N-methyl-6-{3-[(2-piperidin-1-ylethyl)oxy]phenyl}pyrazine-2-carboxamide 189 3-amino-N-methyl-6-{3-[({[3-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide1903-amino-6-(3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide 1913-amino-N-methyl-6-{3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}pyrazine-2-carboxamide 1923-amino-N-methyl-6-(3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide 1933-amino-6-[3-({2-[4-(2-hydroxyethyl)piperazin-1-yl]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide 1943-amino-6-(3-{[2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide 195 ethyl4-{2-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)oxy]ethyl}piperazine-1-carboxylate 1963-amino-N-methyl-6-[3-({[(3S)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1973-amino-N-methyl-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1983-amino-N-methyl-6-[3-({[2-(phenyloxy)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 199 3-amino-N-methyl-6-{3-[({2-[4-(phenylmethyl)piperazin-1-yl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2003-amino-N-methyl-6-{3-[({[1-(phenylmethyl)piperidin-4-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2013-amino-6-(3-{[(furan-3-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 202 3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2033-amino-6-(3-{[(furan-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 204 3-amino-N-methyl-6-{3-[({[4-(phenylmethyl)morpholin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2053-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2063-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2073-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2083-amino-6-[3-({[(6-fluoro-4H-1,3-benzodioxin-8-yl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2093-amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide 2103-amino-6-(3-{[(3,4-dichlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide 211 3-amino-N-methyl-6-[3-({[4-(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide 2123-amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2133-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2143-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2153-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 216 3-amino-N-methyl-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide2173-amino-N-methyl-6-(3-{[(2-methylpropyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 218 3-amino-N-methyl-6-(3-{[({3-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2193-amino-6-(3-{[(cyclopropylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2203-amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2213-amino-N-methyl-6-(3-{[(4-methylphenyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2223-amino-N-methyl-6-[3-({[4-(methyloxy)phenyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2233-amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2243-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 225 3-amino-N-methyl-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2263-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 227 3-amino-N-methyl-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 228 3-amino-6-{3-[({[4-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 229 3-amino-6-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2303-amino-6-[3-({[(4-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2313-amino-6-[3-({[(2-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2323-amino-6-[3-({[(3-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2333-amino-N-methyl-6-pyrimidin-5-ylpyrazine-2-carboxamide 2343-amino-N-methyl-6-[3-(methylsulfonyl)phenyl]pyrazine-2-carboxamide 2353-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2-carboxamide 2363-amino-6-(4-hydroxyphenyl)-N-methylpyrazine-2-carboxamide 2373-amino-6-{3-[({[4-(aminosulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2383-amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2393-amino-6-[3-({[(3-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2403-amino-6-(4-chloro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 241 methyl3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate 242methyl 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate 2433-amino-6-[3-({[(2,3-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2443-amino-6-{3-[({[4-hydroxy-3-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2453-amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2463-amino-6-{3-[({[2-(ethyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2473-amino-6-{3-[({[2-chloro-6-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2483-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2493-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2503-amino-6-[3-({[(2-chloro-6-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 251 3-amino-N-methyl-6-[3-({[(2,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2523-amino-6-(3-{[(2,2-dimethylpropyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2533-amino-6-(3-{[(cyclopentylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2543-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 255 3-amino-N-methyl-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide2563-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2573-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 258 3-amino-N-methyl-6-{3-[({[2,4,6-tris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide259 3-amino-N-methyl-6-[3-({[(3-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2603-amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2613-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2623-amino-6-{3-[({[3,5-bis(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2633-amino-6-(3-{[(2,2-diphenylethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 264 3-amino-N-methyl-6-(3-thienyl)pyrazine-2-carboxamide 2653-amino-N-methyl-6-(3-{[(phenylmethyl)amino]sulfonyl}phenyl)pyrazine-2-carboxamide 2665,5′-diamino-N,N′-dimethyl-2,2′-bipyrazine-6,6′-dicarboxamide 2673-amino-6-(1H-indol-5-yl)-N-methylpyrazine-2-carboxamide 2683-amino-N-methyl-6-(2-thienyl)pyrazine-2-carboxamide 2693-amino-N-methyl-6-pyridin-4-ylpyrazine-2-carboxamide 2703-amino-N-cyclopropyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2713-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-cyclopropylpyrazine-2-carboxamide 2723-amino-N-ethyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2733-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-ethylpyrazine-2-carboxamide 2743-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2753-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2763-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2773-amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2783-amino-6-{3-[(cyclopropylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2793-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2803-amino-6-[3-({[(4′-fluorobiphenyl-2-yl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 281 3-amino-N-methyl-6-[3-({[(2,3,4-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2823-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2833-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2843-amino-6-{3-[(9H-fluoren-9-ylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 285 3-amino-N-methyl-6-[3-({[(2-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2863-amino-6-[3-({[(3,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2873-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2883-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2893-amino-6-[3-({[(2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2903-amino-N-methyl-6-{3-[({[4-(4-methylpiperazin-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2913-amino-6-(4-fluoro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 292 3-amino-N-methyl-6-[3-({[(2,4,6-trichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2933-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2943-amino-6-{3-[({[2,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2953-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 296 3-amino-6-[3-({[(2-chloro-6-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide2973-amino-6-[3-({[(2-chloro-3,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2983-amino-6-[3-({[(2,3-difluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2993-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3003-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 301 3-amino-6-[3-({[(6-chloro-2-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide302 3-amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3033-amino-6-[3-({[(3-chloro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3043-amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3053-amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 306 3-amino-N-methyl-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3073-amino-N-methyl-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3083-amino-N-methyl-6-(3-{[(phenylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3093-amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3103-amino-6-[3-({[(2,5-difluorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 311 3-amino-N-methyl-6-(3-{[(naphthalen-2-ylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3123-amino-N-methyl-6-(3-{[(phenylmethyl)thio]methyl}phenyl)pyrazine-2-carboxamide 3133-amino-N-methyl-6-(3-{[(phenylmethyl)sulfonyl]methyl}phenyl)pyrazine-2-carboxamide 3143-amino-N-methyl-6-(3-{[(phenylmethyl)oxy]methyl}phenyl)pyrazine-2-carboxamide 3153-amino-N-methyl-6-(3-{[(phenylmethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 316 3-amino-N-methyl-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3179H-fluoren-9-ylmethyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate 318 phenylmethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- yl}phenyl)carbamate 319ethyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate320 3-amino-6-[3-({[(3,4-dichlorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 321 1,1-dimethylethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- yl}phenyl)carbamate 322(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate 3233-amino-6-[3-({[(4-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3243-amino-N-methyl-6-(3-{[({4-[(2-morpholin-4-ylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide325 3-amino-N-methyl-6-{3-[({[2-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide326 3-amino-6-[3-({[(3-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3273-amino-6-[3-({[(2-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3283-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2-carboxamide 3293-amino-N-(2-hydroxyethyl)-6-(3-methylphenyl)pyrazine-2-carboxamide 3303-amino-N-methyl-6-(3-{[(phenylacetyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3313-amino-6-[3-({[(4-chlorophenyl)acetyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3323-amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 333 3-amino-6-{3-[({[2-chloro-5-(trifluoromethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 334N-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)methyl]-1H-indole-2-carboxamide 3353-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3363-amino-6-(3-{[(1H-indol-3-ylacetyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3373-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3383-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3393-amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3403-amino-6-[3-({[(3-iodophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3413-amino-N-methyl-6-[3-({[(2-morpholin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3423-amino-N-methyl-6-(3-{[({3-[(2-morpholin-4-ylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide343 3-amino-N-methyl-6-[3-({[(4-morpholin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3443-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3453-amino-N-methyl-6-{3-[({[4-(1-methylethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide346 3-amino-N-methyl-6-(3-{[({[4-(1-methylethyl)phenyl]oxy}acetyl)amino]methyl}phenyl)pyrazine-2-carboxamide347 3-amino-6-{3-[({[(4-aminophenyl)thio]acetyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 348 3-amino-N-methyl-6-(4-(methyloxy)-3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3493-amino-N-methyl-6-(5-{[(phenylmethyl)amino]carbonyl}pyridin-3-yl)pyrazine-2-carboxamide 3503-amino-6-[3-({[(4-iodophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 351 3-amino-N-methyl-6-[3-({[(4-pentylphenyl)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide 3523-amino-6-(3-{[(1,3-benzodioxol-5-ylcarbonyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3533-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3543-amino-N-methyl-6-(3-{[({1-[5-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3553-amino-N-methyl-6-[3-({[(2-piperidin-1-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3563-amino-N-methyl-6-{3-[({[2-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide357 1,1-dimethylethyl(3R)-3-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}pyrrolidine-1-carboxylate 3583-amino-N-methyl-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 359 3-{[(4-chlorophenyl)methyl]amino}-6-{3-[({(3R)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3603-amino-6-{3-[({(3R)-1-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 361N-methyl-3-({[3-(methyloxy)phenyl]methyl}amino)-6-(3-{[((3R)-1-{[3-(methyloxy)phenyl]methyl}pyrrolidin-3-yl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3623-amino-6-{3-[({(3R)-1-[(2,6-dichlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 363N-methyl-3-[(phenylmethyl)amino]-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 364 1,1-dimethylethyl3-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)pyrrolidine-1-carboxylate 3651,1-dimethylethyl 2-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)pyrrolidine-1-carboxylate 3663-amino-N-methyl-6-(3-{[(pyrrolidin-3-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3673-amino-N-methyl-6-(3-{[(pyrrolidin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3683-amino-6-(2-fluoro-5-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3693-amino-6-{3-[(1,3-benzodioxol-5-ylacetyl)amino]phenyl}-N-methylpyrazine-2-carboxamide 3703-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3713-amino-6-{3-[({[3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3723-amino-N-methyl-6-{3-[(phenylmethyl)amino]phenyl}pyrazine-2-carboxamide373 3-amino-N-methyl-6-(3-{[({2-[(2-morpholin-4-ylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide374 3-amino-N-methyl-6-{3-[({[4-(1-methylethyl)phenyl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide375 3-amino-6-[3-({[(4-butylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3763-amino-N-methyl-6-{3-[({[4-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3773-amino-N-methyl-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3783-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 3793-amino-N-methyl-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3803-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3813-amino-6-[3-({[(2-amino-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3823-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3833-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3843-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 385 3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3863-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3873-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3883-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3893-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 390 3-amino-N-methyl-6-[3-({[(2-pyridin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3913-amino-N-methyl-6-[3-({[(2-pyridin-3-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3923-amino-N-methyl-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide3933-amino-6-(3-{[(2,2-diphenylethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 394 3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-3-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3953-amino-N-methyl-6-{3-[({[3-(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 3963-amino-6-[3-({[(4-aminophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 397 3-amino-N-methyl-6-{3-[({[4-(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 3983-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 3993-amino-6-[3-({[(2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4003-amino-6-[5-({[(2,6-difluorophenyl)methyl]amino}carbonyl)pyridin-3-yl]-N-methylpyrazine-2-carboxamide 4013-amino-6-(5-{[(biphenyl-2-ylmethyl)amino]carbonyl}pyridin-3-yl)-N-methylpyrazine-2-carboxamide 4023-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4033-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4043-amino-N-methyl-6-[3-({[(2-piperidin-1-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4053-amino-6-{3-[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 406 3-amino-N-methyl-6-{3-[({[6-(trifluoromethyl)pyridin-3-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 4073-amino-6-[3-(1H-benzimidazol-2-yl)phenyl]-N-methylpyrazine-2-carboxamide408 3-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4093-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4103-amino-N-methyl-6-{3-[(2-phenylethyl)amino]phenyl}pyrazine-2-carboxamide4113-amino-6-(5-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}pyridin-3-yl)-N-methylpyrazine-2-carboxamide 412 3-amino-N-methyl-6-[3-({[2-(phenylamino)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 4133-amino-6-[3-({[(4-ethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 414 3-amino-N-methyl-6-[3-({[(4-pyridin-3-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 4153-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 4163-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylmethyl)phenyl]-N-methylpyrazine-2-carboxamide 4173-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4183-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 419 3-amino-N-methyl-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4203-amino-N-methyl-6-[3-({[(1R)-1-phenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4213-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4223-amino-N-methyl-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 4233-amino-N-methyl-6-{3-[({[3-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 4243-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 4253-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 426 3-amino-N-methyl-6-{3-[({[3-(trifluoromethyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide4273-amino-N-methyl-6-[3-({[(1S)-1-phenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4283-amino-6-[3-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 429 methyl(2S)-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)methyl]amino}(phenyl)ethanoate 4303-amino-6-(3-{[2-(2,5-difluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 4313-amino-N-methyl-6-(3-{[2-(2,3,5,6-tetrafluoro-4-methylphenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide 4323-amino-6-(3-{[2-(2-fluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 4333-amino-6-(3-{[2-(2,4-difluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 434 3-amino-N-methyl-6-(3-{[2-(2,3,5,6-tetrafluorophenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide 4353-amino-N-methyl-6-[3-({[(5-methylpyrazin-2-yl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4363-amino-N-methyl-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 4373-amino-N-methyl-6-[3-({[(3S)-1-(phenylmethyl)pyrrolidin-3-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4383-amino-N-methyl-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4393-amino-6-(3-{[ethyl(phenylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 440 3-amino-N-methyl-6-[3-({[(1S,2S)-2-phenylcyclopropyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4413-Amino-6-(3-benzylcarbamoyl-phenyl)-pyrazine-2-carboxylic acidmethylamide 4423-amino-N-methyl-6-[3-(4-phenyl-1H-imidazol-2-yl)phenyl]pyrazine-2-carboxamide 443 3-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4443-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4453-amino-N-methyl-6-(3-{[(2R)-1,2,3,4-tetrahydronaphthalen-2-ylamino]methyl}phenyl)pyrazine-2-carboxamide 4463-amino-N-methyl-6-(3-{[(1-methyl-1-phenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 4473-amino-6-{3-[(9H-fluoren-9-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 4483-amino-N-methyl-6-{3-[(naphthalen-1-ylamino)methyl]phenyl}pyrazine-2-carboxamide 4493-amino-6-[3-({[(3-fluorobiphenyl-4-yl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4503-amino-6-{3-[({[2-fluoro-4-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 4513-amino-6-[3-({[(2-fluoro-4-furan-2-ylphenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4523-amino-N-methyl-6-{3-[(naphthalen-2-ylamino)methyl]phenyl}pyrazine-2-carboxamide 4533-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4543-amino-N-methyl-6-(3-{[(2S)-1,2,3,4-tetrahydronaphthalen-2-ylamino]methyl}phenyl)pyrazine-2-carboxamide 455 methyl3-amino-6-(3-{[(4,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxylate 4563-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4573-amino-6-{3-[({[2-fluoro-5-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 4583-amino-6-[3-({[(4-ethenyl-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4593-amino-6-(3-{[(4,7-difluoro-3-methyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4603-amino-N-methyl-6-[3-({[(1S,2R)-2-(methyloxy)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4613-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4623-amino-6-[3-({[(2S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4633-amino-6-[3-({[(2R)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4643-amino-6-(3-{[(5-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4653-amino-6-[3-({[(2S)-5-bromo-2,3-dihydro-1H-inden-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4663-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4673-amino-6-(3-{[(4-fluoro-1-hydroxy-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4683-amino-N-methyl-6-[3-({[(1R,2S)-2-(methyloxy)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4693-amino-6-(3-{[(4,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4703-amino-6-(3-{[(6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4713-amino-N-methyl-6-(3-{[(3-oxo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide 4723-amino-6-(3-{[(5-furan-2-yl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4733-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4743-amino-6-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4753-amino-6-(3-{[(6-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4763-amino-6-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4773-amino-6-(3-{[(5-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4783-amino-N-methyl-6-[3-({[5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4793-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4803-amino-6-(3-{[(5-furan-3-yl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4813-amino-N-methyl-6-[3-({[5-(3-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4823-amino-6-[3-({[(1S)-4-fluoro-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4833-amino-6-[3-({[(1S)-5,7-difluoro-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4843-amino-6-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4853-amino-6-(3-{[(6-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4863-amino-6-(3-{[(4,6-dichloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4873-amino-6-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4883-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide 4893-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide 4903-amino-N-methyl-6-[3-({[(1S)-5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4913-amino-N-methyl-6-(3-{[(5-phenyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide 4923-amino-6-(3-{[(4-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4933-amino-N-methyl-6-(3-{[(4-phenyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide 4943-amino-N-methyl-6-[3-({[4-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4953-amino-N-methyl-6-[3-({[6-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4963-amino-N-methyl-6-[3-({[5-(4-methyl-2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4973-amino-N-methyl-6-[3-({[(2R)-6-phenyl-1,2,3,4-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4983-amino-N-methyl-6-naphthalen-2-ylpyrazine-2-carboxamide 4993-amino-N-methyl-6-{3-[({(1S,2S)-2-[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide500 3-amino-6-{3-[(cyclopentylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 5013-amino-6-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 5023-amino-6-(3-{[(7-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 5033-amino-N-methyl-6-quinolin-3-ylpyrazine-2-carboxamide 5043-amino-6-[3-(1H-imidazol-1-ylmethyl)phenyl]-N-methylpyrazine-2-carboxamide5053-amino-N-methyl-6-{3-[({5-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide 5063-amino-N-methyl-6-{3-[({(1R,2R)-2-[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide507 3-amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 5083-amino-6-{3-[({5-[(cyanomethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 5092-amino-5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5103-amino-N-methyl-6-[3-({[5-(4-methylphenyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 5113-amino-6-[3-({[2-(dimethylamino)-1-phenylethyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 5123-amino-N-methyl-6-[3-({[5-(1H-1,2,4-triazol-1-yl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide 5133-amino-6-(3-{[(5-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 5143-amino-N-methyl-6-{3-[({4-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide 5153-amino-6-(3-{[(4-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 5163-amino-N-methyl-6-{1-[(phenylmethyl)amino]isoquinolin-7-yl}pyrazine-2-carboxamide 517 3-amino-N-methyl-6-(3-{[(2-morpholin-4-yl-1-phenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 5183-amino-N-methyl-6-(3-{[(1-phenyl-2-pyrrolidin-1-ylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 5192-amino-5-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5202-amino-5-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5212-amino-5-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5222-amino-5-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5232-amino-5-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5242-amino-5-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5253-amino-6-{1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]isoquinolin-7-yl}-N-methylpyrazine-2-carboxamide 5263-amino-6-{3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,3-dihydro-1H-inden-5-yl}-N-methylpyrazine-2-carboxamide 5273-amino-6-[3-({[6-(3-hydroxypropyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 5285-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(1,3-oxazol-5-yl)pyrazin-2-amine 5293-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carbohydrazide 5303-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 5311-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-yl]ethanone 5323-amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)methyl]phenyl}-N-(naphthalen-2-ylmethyl)pyrazine-2-carboxamide 5333-amino-N-cyclohexyl-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)methyl]phenyl}pyrazine-2-carboxamide 5343-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(pyridin-4-ylmethyl)pyrazine-2-carboxamide 535{3-[5-amino-6-(4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol 5365-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4H-1,2,4-triazol-3-yl)pyrazin-2-amine 5373-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2,2,2-trifluoroethyl)pyrazine-2-carboxamide 5383-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(5-hydroxypentyl)pyrazine-2-carboxamide 5393-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(4-hydroxybutyl)pyrazine-2-carboxamide 5403-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-pyrrolidin-1-ylethyl)pyrazine-2-carboxamide 5413-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-piperidin-1-ylethyl)pyrazine-2-carboxamide 5423-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-morpholin-4-ylethyl)pyrazine-2-carboxamide 5433-amino-N-(cyclopropylmethyl)-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino}methyl}phenyl)pyrazine-2-carboxamide 5443-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(phenylmethyl)pyrazine-2-carboxamide 5453-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-phenylethyl)pyrazine-2-carboxamide 546[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-yl](phenyl)methanone 5473-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-hydroxyethyl)pyrazine-2-carboxamide 5483-amino-N-cyclopropyl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 5495-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(pyrrolidin-1-ylcarbonyl)pyrazin-2-amine 550{3-[5-amino-6-(5-methyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol551{3-[5-amino-6-(5-phenyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol552 (3-{5-amino-6-[5-(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol 5533-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N′-methylpyrazine-2-carbohydrazide 5543-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N,N-dimethylpyrazine-2-carboxamide 5555-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine 5563-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(dimethylamino)ethyl]pyrazine-2-carboxamide 5575-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-phenyl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 5583-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide 5593-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(methylamino)ethyl]pyrazine-2-carboxamide 5603-{5-amino-6-[(3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 5613-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-hydroxypropyl)pyrazine-2-carboxamide 562 1,1-dimethylethyl4-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate 563 1,1-dimethylethyl 4-[({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]piperidine-1-carboxylate 5643-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-piperidin-4-ylpyrazine-2-carboxamide 5653-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-(piperidin-4-ylmethyl)pyrazine-2-carboxamide 5663-[5-amino-6-(morpholin-4-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide567 1,1-dimethylethyl 3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 5683-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-pyrrolidin-3-ylpyrazine-2-carboxamide 569(3-{5-amino-6-[5-(1,1-dimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol 570{3-[5-amino-6-(5-furan-2-yl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol571[3-(5-amino-6-{5-[3-(methyloxy)phenyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)phenyl]methanol 5722-({3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2-yl}carbonyl)-N-phenylhydrazinecarboxamide 5733-{5-amino-6-[(4-methylpiperazin-1-yl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 5743-(5-amino-6-{[4-(4-fluorophenyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 5753-(5-amino-6-{[4-(phenylmethyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 576 methylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glycinate 577N-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glycine 5783-{5-amino-6-[(3,5-difluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 5793-[5-amino-6-(biphenyl-4-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide580{3-[5-amino-6-(3-pyridin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol581 (3-{5-amino-6-[3-(4-chlorophenyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol 5825-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1,1-dimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine 583(3-{5-amino-6-[3-(2-thienyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol584 5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[3-(methyloxy)phenyl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 5853-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(dimethylamino)propyl]pyrazine-2-carboxamide 5863-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(1H-imidazol-1-yl)propyl]pyrazine-2-carboxamide 5873-{5-amino-6-[(4-chloro-3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 5883-(5-amino-6-{[2,4-bis(methyloxy)phenyl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 5893-(5-amino-6-{[4-(dimethylamino)phenyl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 590 methyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-L-prolinate 591 methyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidine-3-carboxylate 592 1,1-dimethylethyl4-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperazine-1-carboxylate 5933-[5-amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide594 N-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glutamic acid 5955-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{5-[(methyloxy)methyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-amine 5965-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 5973-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(methylamino)propyl]pyrazine-2-carboxamide 5983-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-pyrrolidin-1-ylpropyl)pyrazine-2-carboxamide 5993-(5-amino-6-{(1E)-N-[4-(methyloxy)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6003-(5-amino-6-{(1E)-N-[4-(1-methylethyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6013-{5-amino-6-[(1E)-N-1,3-benzothiazol-2-ylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6023-{5-amino-6-[(1E)-N-(4-methylphenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6033-{5-amino-6-[(1E)-N-(4-chlorophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6043-{5-amino-6-[(1E)-N-methyl-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6053-{5-amino-6-[(1E)-N-(2-hydroxyethyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 606{3-[5-amino-6-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol607 {3-[5-amino-6-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol 6083-[5-amino-6-(2-aminopyrimidin-4-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide609 3-{5-amino-6-[2-(dimethylamino)pyrimidin-4-yl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 610 ethylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-L-tyrosinate 611N-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-D-tyrosine 612 1,1-dimethylethyl [3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)propyl]carbamate 613 3-amino-N-(3-aminopropyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6141-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidine-3-carboxylic 615 1,1-dimethylethyl[2-({[3-amino-6-(3- {[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)ethyl]carbamate 616 3-amino-N-(2-aminoethyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6171,1-dimethylethyl (1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidin-4-yl)carbamate 6183-{5-amino-6-[(4-aminopiperidin-1-yl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6193-{5-amino-6-[imino(2-phenylhydrazino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6203-{5-amino-6-[imino(morpholin-4-ylamino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6213-(5-amino-6-{imino[(4-methylpiperazin-1-yl)amino]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6223-{5-amino-6-[imino(piperidin-1-ylamino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6233-{5-amino-6-[(azepan-1-ylamino)(imino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6243-{5-amino-6-[imino({(2R)-2-[(methyloxy)methyl]pyrrolidin-1-yl}amino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 625{3-[5-amino-6-(3-piperidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol 6263-{5-amino-6-[(1E)-N-morpholin-4-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6274-((2E)-2-{1-[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]ethylidene}hydrazino)benzoic acid 628 ethyl((2E)-2-{1-[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]ethylidene}hydrazino)acetate 6293-{5-amino-6-[(1E)-N,N-dimethylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6303-(5-amino-6-{(1E)-N-[4-(methylsulfonyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6313-{5-amino-6-[(1E)-N-(4-cyanophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6323-{5-amino-6-[(1E)-N-pyridin-2-ylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6333-(5-amino-6-{(1E)-N-[amino(imino)methyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 634 3-[5-amino-6-((1E)-N-{4-[(trifluoromethyl)oxy]phenyl}ethanehydrazonoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6353-(5-Amino-6-{1-[(4-nitro-phenyl)-hydrazono]-ethyl}-pyrazin-2-yl)-N-benzyl-benzamide 636 3-(5-amino-6-{(1E)-N-[4-(trifluoromethyl)pyrimidin-2-yl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6373-{5-amino-6-[(1E)-N-1H-1,2,3-benzotriazol-1-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6383-{5-amino-6-[(1E)-N-methylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6395-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 6403-(5-amino-6-{(1E)-N-[4-(trifluoromethyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6413-{5-amino-6-[(1E)-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6423-{5-amino-6-[(1E)-N-(4-methylpiperazin-1-yl)ethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 643{3-[5-amino-6-(3-pyrrolidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol 6443-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 6453-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-pyrrolidin-3-yl]pyrazine-2-carboxamide 6463-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamide 647N-[3-(acetylamino)propyl]-3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6483-amino-N-{3-[(furan-2-ylcarbonyl)amino]propyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6493-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamide 6503-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-4-ylcarbonyl)amino]propyl}pyrazine-2-carboxamide 651N-[3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)propyl]quinoxaline-2-carboxamide 6523-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[3-({[6-(trifluoromethyl)pyridin-3-yl]carbonyl}amino)propyl]pyrazine-2-carboxamide6533-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(quinolin-8-ylsulfonyl)amino]propyl}pyrazine-2-carboxamide 6543-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-2-ylsulfonyl)amino]propyl}pyrazine-2-carboxamide 6553-amino-N-[3-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)propyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6563-[5-amino-6-(2-methylpyrimidin-4-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide657 3-{5-amino-6-[2-(methylamino)pyrimidin-4-yl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6583-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-4-ylcarbonyl)amino]ethyl}pyrazine-2-carboxamide 6593-amino-N-{2-[(furan-2-ylcarbonyl)amino]ethyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 660N,N′-cyclohexane-1,2-diylbis[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide] 661N-[2-(acetylamino)ethyl]-3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6623-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(quinolin-8-ylsulfonyl)amino]ethyl}pyrazine-2-carboxamide 663N-[2-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)ethyl]quinoxaline-2-carboxamide 6643-amino-N-(2-{[(2-chloropyridin-3-yl)carbonyl]amino}ethyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6653-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-2-ylsulfonyl)amino]ethyl}pyrazine-2-carboxamide 6663-amino-N-[2-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)ethyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6673-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide668 3-[5-amino-6-(imino{2-[4-(trifluoromethyl)pyrimidin-2-yl]hydrazino}methyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6693-{5-amino-6-[[2-(1,3-benzothiazol-2-yl)hydrazino](imino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6703-[5-amino-6-(1,5-diphenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6713-[5-amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6723-[5-amino-6-(1-methyl-5-phenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6733-[5-amino-6-((1E)-N-{(2R)-2-[(methyloxy)methyl]pyrrolidin-1-yl}ethanimidoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6743-{5-amino-6-[(1E)-N-azepan-1-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6753-(5-amino-6-{(E)-[(phenylmethyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6763-[5-amino-6-((E)-{[amino(imino)methyl]hydrazono}methyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6773-(5-amino-6-{(E)-[(2-hydroxyethyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6783-{5-amino-6-[(E)-(pyridin-2-ylhydrazono)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6793-(5-amino-6-{(E)-[(4-cyanophenyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6803-(5-amino-6-{(E)-[(4-methylphenyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6813-{5-amino-6-[(E)-(hydroxyimino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 682{3-[5-amino-6-(3-pyridin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol6835-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-piperidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 6843-amino-N-[3-({[4-(dimethylamino)phenyl]carbonyl}amino)propyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6853-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 686 1,1-dimethylethyl4-[(3S)-3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]piperidine-1-carboxylate 6873-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-piperidin-4-ylpyrrolidin-3-yl]pyrazine-2-carboxamide 688 1,1-dimethylethyl(2R)-2-{[(3S)-3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]methyl}pyrrolidine-1-carboxylate 6893-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{(3S)-1-[(2R)-pyrrolidin-2-ylmethyl]pyrrolidin-3-yl}pyrazine-2-carboxamide 6903-amino-N-((3S)-1-{[4-(dimethylamino)phenyl]methyl}pyrrolidin-3-yl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6913-amino-N-{2-[({[4-(dimethylamino)phenyl]amino}carbonyl)amino]ethyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6923-amino-N-[2-({[4-(dimethylamino)phenyl]carbonyl}amino)ethyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6933-{5-amino-6-[imino(2-pyridin-2-ylhydrazino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 6943-[5-amino-6-(morpholin-4-ylmethyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide695 ethyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]methyl}piperidine-4-carboxylate 6963-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]pyrazine-2-carboxamide 697 methylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}threoninate 698{3-[5-amino-6-(3-piperidin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol 6993-(ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 7003-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 7013-[5-amino-6-(1-methyl-5-piperidin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 7023-[5-amino-6-(5-methyl-1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 703{3-[5-amino-6-(3-morpholin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol 7045-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 7055-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 7063-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide 7076-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-3-(ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide 7083-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide709 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate710 1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 711 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate712 1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 713 1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 7143-amino-6-[3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7153-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7163-amino-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7173-amino-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7183-{5-amino-6-[(2-ethylhydrazino)(imino)methyl]pyrazin-2-yl}-N-(2,3-dihydro-1H-inden-1-yl)benzamide 7193-{5-amino-6-[imino(2-methylhydrazino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 7203-{5-amino-6-[imino(2-phenylhydrazino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 721 phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 722 phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 7235-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 724[3-(5-amino-6-{3-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methanol 725[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methanol 7263-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide7273-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 7281,1-dimethylethyl 3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate7293-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamide 7303-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-(1-ethylpiperidin-3-yl)pyrazine-2-carboxamide 7313-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 732(3-{5-amino-6-[5-(1-ethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol 7335-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1-ethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine 7343-[5-amino-6-(1-ethyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzamide 7353-[5-amino-6-(1-methyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 736(3-{5-amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol 7375-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-amine 7381,1-dimethylethyl (3S)-3-{[(3-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 739 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 740 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 741 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 742 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate7433-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7443-amino-N-[(3S)-pyrrolidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 7453-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7463-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7473-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7483-{5-amino-6-[imino(2-pyridin-4-ylhydrazino)methyl]pyrazin-2-yl}-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzamide 749 phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 7503-amino-6-(3-{(1S)-1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]ethyl}phenyl)-N-methylpyrazine-2-carboxamide 7513-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide752 1,1-dimethylethyl(3S)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrrolidine-1-carboxylate 7533-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide 754 phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 7553-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 756 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 757 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 758 1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 759 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[(3,4-dihydro-2H-chromen-4-ylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate7603-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7613-amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7623-amino-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 763 dimethyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzene-1,3-dicarboxylate 7643-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 7653-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-piperidin-3-yl]pyrazine-2-carboxamide 7663-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-piperidin-3-ylpyrazine-2-carboxamide 7673-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide 7683-amino-N-azepan-4-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 769 1,1-dimethylethyl(3S)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate 770 1,1-dimethylethyl4-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)azepane-1-carboxylate7713-[5-amino-6-(5-{2-[(phenylmethyl)oxy]ethyl}-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 7723-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-4-fluorophenyl)-N-methylpyrazine-2-carboxamide 7733-[5-amino-6-(1-phenyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 7743-{5-amino-6-[amino(imino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 7753-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]benzamide 7761,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate777 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate 7783-amino-6-{3-[(3,4-dihydro-2H-chromen-4-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7793-amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7803-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide781 1,1-dimethylethyl4-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]azepane-1-carboxylate7823-amino-N-azepan-4-yl-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 7833-amino-N-azepan-4-yl-6-{3-[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2-d][1,3]oxazol-2-yl]phenyl}pyrazine-2-carboxamide 784 1,1-dimethylethyl(3R)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrrolidine-1-carboxylate 7853-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide 786 1,1-dimethylethyl(3R)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate 7873-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide7883-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-5-fluorophenyl)-N-methylpyrazine-2-carboxamide 7893-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-[(methyloxy)carbonyl]benzoic acid 790 methyl3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}benzoate 7915-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-N′-pyrrolidin-3-ylbenzene-1,3-dicarboxamide 7923-[5-amino-6-(5-phenyl-1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 7933-[5-amino-6-(5-methyl-1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 794 1,1-dimethylethyl(3R)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate795 1,1-dimethylethyl(3R)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate 7963-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 7975-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-N′-[(3R)-pyrrolidin-3-yl]benzene-1,3-dicarboxamide 798(3-{5-amino-6-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol 7993-[5-amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 800 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 8013-amino-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8023-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)pyrazine-2-carboxamide 8033-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamide 8043-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide 8053-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide 8063-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide807 3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide8083-amino-N-[(3S)-pyrrolidin-3-yl]-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 809N-[3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)phenyl]-2-(2,4-dichlorophenyl)acetamide 810 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate8113-amino-6-(3-hydroxyphenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide8123-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8133-[5-amino-6-(1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 8143-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8153-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8163-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8173-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8183-{5-amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}-N-[(2-chloro-6-fluorophenyl)methyl]benzamide 8193-amino-N-1-azabicyclo[2.2.2]oct-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 8203-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(4-chloro-2-fluorophenyl)methyl]benzamide 8213-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2-chlorophenyl)methyl]benzamide 822 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 823 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 8245-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4-piperidin-3-yl-1,3-thiazol-2-yl)pyrazin-2-amine 8253-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8263-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8273-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,6-difluorophenyl)methyl]benzamide 8283-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2-chloro-6-fluorophenyl)methyl]benzamide 8293-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,5-dichlorophenyl)methyl]benzamide 8303-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(3,4-dichlorophenyl)methyl]benzamide 8313-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8323-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 833 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]phenyl}pyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate 8343-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(2-fluorophenyl)methyl]benzamide 8353-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(3-fluorophenyl)methyl]benzamide 8363-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(4-fluorophenyl)methyl]benzamide 8373-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(3-chlorophenyl)methyl]benzamide 8383-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(4-chlorophenyl)methyl]benzamide 8393-amino-6-[3-(aminomethyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8403-amino-6-(3-hydroxyphenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide841 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate 8423-amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8433-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 8443-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8453-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-5-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 8463-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 8473-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8483-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8493-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8503-amino-6-{3-[({[4-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8513-amino-6-(3-{[(naphthalen-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8523-amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8533-amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8543-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 8553-amino-6-{3-[({[2-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8563-amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8573-amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8583-amino-6-[3-({[(2,3-difluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8593-amino-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8603-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide8613-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8623-amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8633-amino-N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 8643-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8653-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,4-difluorophenyl)methyl]benzamide 8663-amino-6-(3-{[(1,2-diphenylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8673-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(3,4-difluorophenyl)methyl]benzamide 8683-amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 869 methyl4-[({[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]carbonyl}amino)methyl]benzoate 8703-amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8713-amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8723-amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 873 3-amino-6-{3-[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 874 3-amino-6-{3-[({[2-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8753-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3R)-pyrrolidin-3-ylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8763-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 8773-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-piperidin-1-ylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 8783-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8793-amino-6-[3-({[(2-methyloxy)ethyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8803-amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8813-amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8823-amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8833-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 8843-amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8853-amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8863-amino-6-(3-{[(2,6-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8873-amino-6-(3-{[(pentafluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8883-amino-6-(3-{[(2-chloro-4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8893-amino-6-[3-({[4-(methylthio)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8903-amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8913-amino-6-[3-({[4-(4-chlorophenyl)-2-thienyl]carbonyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8923-amino-6-[3-({[(4-bromophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8933-amino-6-(3-{[(naphthalen-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8943-amino-6-(3-{[2-(4-phenylpiperazin-1-yl)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 895N-[(3-{5-amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-(4-bromophenyl)urea 896N-[(3-{5-amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-naphthalen-2-ylurea 8973-amino-6-(3-{[(2,4-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8983-amino-6-(3-{[(2-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8993-amino-6-{3-[({5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2-yl}carbonyl)amino]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide9003-amino-6-[3-({[4-(dimethylamino)naphthalen-1-yl]carbonyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9013-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4-(1,2,3-thiadiazol-5-yl)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 9023-amino-6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9033-amino-6-{3-[({[4-(dimethylamino)phenyl]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9043-amino-6-{3-[(2-hydroxyethyl)oxy]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9053-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9063-amino-6-(3-{[(3,4-dihydro-2H-1,5-benzodioxepin-7-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide907 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(quinolin-7-ylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9083-amino-6-[3-({[(biphenyl-4-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9093-amino-6-(3-{[(4-bromo-2-fluorophenyl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 910N-[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]quinoline-3-carboxamide 9113-amino-6-[3-({[6-(methyloxy)-1-benzofuran-3-yl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9123-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 9133-amino-6-[3-({[3,5-bis(trifluoromethyl)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9143-amino-6-{3-[({[(2,4-difluorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9153-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide916 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 917 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2-[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 918 3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide919 3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({2-[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide 9203-amino-6-(3-{[({[2-(methylthio)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9213-amino-6-{3-[({[(3-bromo-5-methylphenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9223-amino-6-{3-[({[(2-bromophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9235-[3-(aminomethyl)phenyl]-3-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 924 3-amino-6-{3-[({[4-(4-methylpiperazin-1-yl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9253-amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9263-amino-6-(3-{[(2-morpholin-4-ylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9273-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2R)-pyrrolidin-2-ylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 9283-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2S)-pyrrolidin-2-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 9293-amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9303-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4-[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide 931 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9323-amino-6-{3-[({[4-(methyloxy)phenyl]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9333-amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9343-amino-6-(3-{[(furan-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9353-amino-6-[3-({[(2,3-dihydro-1,4-benzodioxin-6-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9363-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9373-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9383-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-thienylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9393-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide940N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-2-chlorobenzamide 941N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-chlorobenzamide 942N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-iodobenzamide 943N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-3,5-difluorobenzamide 944N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-bromo-2-fluorobenzamide 945N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-bromo-2-chlorobenzamide 9463-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]-5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-amine 9473-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 9483-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2-(2-thienyl)-1,3-thiazol-4-yl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide 9493-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[5-(2-thienyl)pyridin-3-yl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide 9503-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9513-amino-6-[3-({[(2,4-dichloro-6-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9523-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9533-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-thienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9543-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(3-thienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9553-amino-6-[3-({[(4-chlorophenyl)sulfonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9563-amino-6-[3-({[(1,3-benzodioxol-5-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9573-amino-6-(3-{[({[4-(methyloxy)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9583-amino-6-{3-[({[(4-fluorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9593-amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9603-amino-6-{3-[(2-morpholin-4-ylethyl)oxy]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9613-amino-6-[3-(methyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide9623-amino-6-[3-(ethyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide963 3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 9643-amino-6-(3-{[2-(ethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 965 phenylmethyl4-(2-{[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]oxy}ethyl)piperazine-1-carboxylate 966 3-amino-6-(3-{[({[4-(dimethylamino)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9673-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 9683-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide969 3-amino-6-[3-({[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide 9703-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 9713-amino-6-{3-[({[(4-chlorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9723-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide 9733-amino-N-[(3S)-azepan-3-yl]-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 9743-amino-N-[(3S)-azepan-3-yl]-6-(3-methylphenyl)pyrazine-2-carboxamide9753-amino-6-(3-{[(2-methylphenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 976 3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[3-(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide 9773-amino-6-[3-({[4-(methyloxy)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9783-amino-6-(3-{[(6-methylpyridin-3-yl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9793-amino-6-(3-{[(3-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9803-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3-ylacetyl)amino]phenyl}pyrazine-2-carboxamide 981 3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3-ylcarbonyl)amino]phenyl}pyrazine-2-carboxamide 9823-amino-6-(3-{[(2,5-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9833-amino-6-(3-{[(4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 984 3-amino-6-{3-[({[3-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9853-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9863-Amino-6-[3-({[5-(4-nitro-phenyl)-furan-2-carbonyl]-amino}-methyl)-phenyl]-pyrazine-2-carboxylic acid (3S)-piperidin-3-ylamide 9873-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9883-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)phenyl]pyrazine-2-carboxamide 9893-amino-6-[3-({[(5-methylisoxazol-3-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9903-amino-6-(3-{[(isoxazol-5-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9913-amino-6-[3-({[(4-methyl-1,2,3-thiadiazol-5-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9923-amino-6-[3-({[(2,5-dichloro-3-thienyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9933-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9943-amino-6-{3-[({[2-chloro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9953-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9963-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 9973-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9983-amino-6-{3-[({[2-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9993-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10003-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10013-amino-6-{3-[({[2-fluoro-4-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10023-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10033-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10043-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10053-amino-6-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10063-amino-6-[3-({[(3-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10073-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10083-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10093-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10103-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10113-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10123-amino-6-[3-({[(6-chloro-2-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 1013 3-amino-6-[3-({[(2-chloro-6-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10143-amino-6-[3-({[(2-chloro-3,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10153-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10163-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,4-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10173-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10183-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10193-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10203-amino-N-[(3S)-azepan-3-yl]-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 10213-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10223-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10233-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10243-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10253-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10263-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10273-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10283-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10293-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10303-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10313-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10323-amino-6-[3-({[(3-bromo-5-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10333-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 10343-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10353-amino-6-[3-({[(2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10363-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10373-amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10383-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10393-amino-6-[3-({[(3-methoxyphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10403-amino-6-{3-[({[phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10413-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10423-amino-6-{3-[({[3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10433-amino-N-[(3S)-azepan-3-yl]-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide

Another aspect of the invention is a pharmaceutical compositioncomprising a compound according to any one of paragraphs [0039]-[0080]and a pharmaceutically acceptable carrier.

Another aspect of the invention is a metobolite of the compound or thepharmaceutical composition according to any one of paragraphs[0039]-[0081].

Another aspect of the invention is a method of modulating the in vivoactivity of a kinase, the method comprising administering to a subjectan effective amount of the compound or the pharmaceutical compositionaccording to any of paragraphs [0039]-[0081].

Another aspect of the invention is a method according to paragraph[0083], wherein the kinase is Chk1.

Another aspect of the invention is a method according to paragraph[0084], wherein modulating the in vivo activity of the kinase comprisesinhibition of said kinase.

Another aspect of the invention is a method of treating diseases ordisorders associated with uncontrolled, abnormal, and/or unwantedcellular activities, the method comprising administering atherapeutically effective amount of to a mammal in need thereof and thecompound as described in any one of paragraphs [0039]-[0080].

Another aspect of the invention is a method of inhibiting proliferationof cancerous cells, the method comprising contacting the cells orcausing the cells to be contacted with a cancer therapeutic and thecompound as described in any one of paragraphs [0039]-[0080].

Another aspect of the invention is a method according to paragraph[0087], wherein the cancer therapeutic is a DNA damaging agent.

Yet another aspect of the invention is a method of diminishingproliferation of cancerous cells in a patient, the method comprisingadministering to the patient the compound as described in any one ofparagraphs [0039]-[0008] and one or more cancer therapeutic agents,preferably with a pharmaceutically acceptable carrier. Exemplaryanti-cancer agents suitable for use (including analogs, pharmaceuticallyacceptable forms, such as salts and in liposomes) in this aspect of theinvention are: 1. Topoisomerase I inhibitors: Camptothecin, Topotecan,9-Nitrocamptothecin, 9-Aminocamptothecin, Karenitecin, Irinotecan, andthe like; 2. Topoisomerase II inhibitors: Etoposide, EtoposidePhosphate, Teniposide, Amsacrine, Epipodophyllotoxin derivatives,Razoxane, Dexrazoxane (Zinecard), and the like; 3. Classical Alkylatingagents: Nitrogen Mustards such as Mechlorethamine, Cyclophosphamide,Ifosfamide, Chlorambucil, Melphalan, and the like; Aziridines such as,Thiotepa, Trenimon, Triethylenemelamine, and the like; Epoxides such asDianhydrogalactitol, Dibromodulcitol, and the like; Alkyl AlkaneSulfonates such as Busulfan, dimethylsulfate, and the like; Nitrosoureassuch as Chlorothylnitrosourea, BCNU, CCNU (lomustine), Methyl-CCNU(semustine), Streptozotocin, Chlorozotocin, and the like; Alkylatingagent-steroid conjugates such as Prednimustine(chlorambucil-prednisolone), Estramustine (nornitrogenmustard-estradiol), and the like; 4. Non-classical alkylating agents:Procarbazine, Dacarbazine, Hexamethylmelamine, Pentamethylmelamine,Temozolomide, and the like; 5. Other DNA damaging/binding agents:Cisplatins such as Cisplatin, Carboplatin, Oxaliplatin, Bleomycin, andthe like; Antibiotics such as Dactinomycin, Mithramycin, Mitomycin C,and the like; Anthracyclines/Anthracenediones (note—also considered topoII inhibitors) such as Daunorubicin, Doxorubicin, Epirubicin,Idarubicin, and the like; 6. Antimetabolites: Antifolates such asMethotrexate, Edatrexate, Trimethoprim, Nolatrexed, Raltitrexed(Tomudex), Hydroxyurea, and the like; Nucleic acid analogs such as5-fluorouracil, Ftorafur, Capecitabine, Furtulon, Eniluracil, ara-C(Cytosine arabinose), 5-azacytidine, Gemcitabine, Mercaptopurine,Thioguanine, Pentostatin, and the like; 7. Ribonucleic acid related:Antisense DNA, antisense RNA, antisense DNA/RNA hybrids, ribozymes, andthe like; 8. Radiation: ultraviolet and/or other; 9. Vinca Alkaloids:Vincristine, Vinblastine, and the like; 10. Other anti-cancer agents:those having mechanisms of action that may or may not involve DNAdamage; 11. Taxanes: Paclitaxel, Docetaxel, and the like; 12. Enzymes:L-Asparaginase and the like; 13. Natural Products; 14. MiscellaneousAgents: kinase inhibitors, Imatinib; 15. Mitotane; 16.Aminoglutethimide; 17. Hormones and Antagonists: Diethylstilbestrol,Ethinyl estradiol, Tamoxifen, Anastrozole, Testosterone propionate,Fluoxymesterone, Flutamide, Leuprolide, Prednisone, Hydroxyprogesteronecaproate, Medroxyprogesterone aacetate, Megestrol acetate; 18.Biological Response Modifiers: Interferon-alfa, Interleukin, and thelike.

Other agents suitable for use in combination with a compound of theinvention are disclosed in “Cancer Chemotherapy and Biotherapy:Principles and Practice,” Third edition, B. A. Chabner and D. L. Longo,eds., 2001, Lippincott Williams and Wilkins, Philadelphia, U.S.A.; P.Calabresi and B. A. Chabner, “Chemotherapy of Neoplastic Diseases” in“Goodman and Gilman's The Pharmcological Basis of Therapeutics,” Tenthedition, J. G. Hardman and L. E. Limbird, eds., 2001, McGraw-Hill, NewYork, USA, pp. 1381-1388; and B. A. Chabner, D. P. Ryan, L. Paz-Ares, R.Garcia-Carbonero, and P. Calabresi, “Antineoplastic Agents” in “Goodmanand Gilman's The Pharnacological Basis of Therapeutics,” Tenth edition,J. G. Hardman and L. E. Limbird, eds., 2001, McGraw-Hill, New York, USA,pp. 1389-1459.

Another aspect of the invention is a method of enhancing the efficacy ofa disease therapy that inflicts DNA damage, the method comprisingcombining the disease therapy with administration of a compound orpharmaceutical composition as described in any one of paragraphs[0023]-[0066]. As an example, photochemotherapy of dermatologicalconditions such as psoriasis employs ultraviolet radiation incombination with psoralen type photosensitizers to cause DNA damage. Inone embodiment of this aspect of the invention, such photochemotherapyis combined with administration of a compound or pharmaceuticalcomposition as described in any one of paragraphs [0039]-[0081].

Definitions

As used in the present specification, the following words and phrasesare generally intended to have the meanings as set forth below, exceptto the extent that the context in which they are used indicatesotherwise or they are expressly defined to mean something different.

“Alkyl” is intended to include linear, branched, or cyclic hydrocarbonstructures and combinations thereof, inclusively. For example, “C₈alkyl” may refer to an n-octyl, iso-octyl, cyclohexylethyl, and thelike. Lower alkyl refers to alkyl groups of from one to eight carbonatoms. Examples of lower alkyl groups include methyl, ethyl, propyl,isopropyl, butyl, s-butyl, t-butyl, isobutyl, pentyl, cyclopentyl,hexyl, cyclohexyl, and the like. Higher alkyl refers to alkyl groupscontaining more that 6 carbon atoms. Exemplary alkyl groups are those ofC₂₀ or below. Cycloalkyl is a subset of alkyl and includes cyclichydrocarbon groups of from 3 to 13 carbon atoms. Examples of cycloalkylgroups include c-propyl, c-butyl, c-pentyl, norbornyl, adamantyl and thelike. Cycloalkyl rings may have unsaturation but are not aromatic. Inthis application, alkyl refers to alkanyl, alkenyl, and alkynyl residues(and combinations thereof); it is intended to include cyclohexylmethyl,vinyl, allyl, isoprenyl, and the like. Thus when an alkyl residue havinga specific number of carbons is named, all geometric isomers having thatnumber of carbons are intended to be encompassed; thus either “butyl” or“C₄alkyl” is meant to include n-butyl, sec-butyl, isobutyl, t-butyl,isobutenyl and but-2-yne radicals, for example; “propyl” or “C₃alkyl”each include n-propyl, propenyl, and isopropyl, for example. Alkyls withvariable numbers of carbons may be named by using number ranges assubscripts, as for example, lower alkyl is equivalent to C₁₋₈alkyl.

“Alkylene” refers to straight or branched chain divalent radicalconsisting solely of carbon and hydrogen atoms, containing nounsaturation and having from one to ten carbon atoms, e.g., methylene,ethylene, propylene, n-butylene and the like. Alkylene is a subset ofalkyl, referring to the same residues as alkyl, but having two points ofattachment and specifically fully saturated. Examples of alkyleneinclude ethylene (—CH₂CH₂—), propylene (—CH₂CH₂CH₂—),2-dimethylpropylene (—CH₂C(CH₃)₂CH₂—), cyclohexylpropylene (—CH₂CH(C₆H₁₃)CH₂—).

“Alkylidene” refers to a straight or branched chain unsaturated divalentradical consisting solely of carbon and hydrogen atoms, having from twoto ten carbon atoms, e.g., ethylidene, propylidene, n-butylidene, andthe like. Alkylidene is a subset of alkyl, referring to the sameresidues as alkyl, but having two points of attachment and specificallydouble bond unsaturation. The unsaturation present includes at least onedouble bond and a double bond can exist between the first carbon of thechain and a carbon atom of the rest of the molecule to which it isattached.

“Alkylidyne” refers to a straight or branched chain unsaturated divalentradical consisting solely of carbon and hydrogen atoms having from twoto ten carbon atoms, e.g., propylid-2-ynyl, n-butylid-1-ynyl, and thelike. Alkylidyne is a subset of alkyl, referring to the same residues asalkyl, but having two points of attachment and specifically triple bondunsaturation. The unsaturation present includes at least one triple bondand a triple bond can exist between the first carbon of the chain and acarbon atom of the rest of the molecule to which it is attached.

Any of the above radicals, “alkylene,” “alkylidene” and “alkylidyne,”when optionally substituted, may contain alkyl substitution which itselfcontains unsaturation. For example,2-(2-phenylethynyl-but-3-enyl)-naphthalene (IUPAC name) contains ann-butylid-3-ynyl radical with a vinyl substituent at the 2-position ofsaid radical.

“Alkoxy” refers to the group —O-alkyl, for example including carbonatoms of a straight, branched, cyclic configuration, unsaturated chains,and combinations thereof attached to the parent structure through anoxygen atom. Examples include methoxy, ethoxy, propoxy, isopropoxy,cyclopropyloxy, cyclohexyloxy and the like. Lower-alkoxy refers togroups containing one to eight carbons.

“Substituted alkoxy” refers to the group —O-(substituted alkyl), thesubstitution on the alkyl group generally containing more than onlycarbon (as defined by alkoxy). One exemplary substituted alkoxy group is“polyalkoxy” or —O— (optionally substituted alkylene)-(optionallysubstituted alkoxy), and includes groups such as —OCH₂CH₂OCH₃, andglycol ethers such as polyethyleneglycol and —O(CH₂CH₂O)_(x)CH₃, where xis an integer of between about 2 and about 20, in another example,between about 2 and about 10, and in a further example between about 2and about 5. Another exemplary substituted alkoxy group is hydroxyalkoxyor —OCH₂(CH₂)_(y)OH, where y is for example an integer of between about1 and about 10, in another example y is an integer of between about 1and about 4. Thus, where a group is defined as —OR, where “R” isoptionally substituted alkyl, then such a group would include, but notbe limited to, hydroxyalkoxy, polyalkoxy, and the like.

“Alkoxyl” refers to an alkoxy as a linking group, for example —OCH₂— andthe like. Lower alkoxyl then refers to groups containing one to eightcarbons and an oxygen.

“Substituted alkoxyl” refers to a linking group alkoxy, for example—OCH₂CH₂OCH₂—. Optionally substituted alkoxyl refers to both alkoxyl andsubstituted alkoxyls.

“Acyl” refers to groups of from one to ten carbon atoms of a straight,branched, cyclic configuration, saturated, unsaturated and aromatic andcombinations thereof, attached to the parent structure through acarbonyl functionality. One or more carbons in the acyl residue may bereplaced by nitrogen, oxygen or sulfur as long as the point ofattachment to the parent remains at the carbonyl. Examples includeacetyl, benzoyl, propionyl, isobutyryl, t-butoxycarbonyl,benzyloxycarbonyl and the like. Lower-acyl refers to groups containingone to eight carbons.

“α-Amino Acids” refer to naturally occurring and commercially availableamino acids and optical isomers thereof. Typical natural andcommercially available α-amino acids are glycine, alanine, serine,homoserine, threonine, valine, norvaline, leucine, isoleucine,norleucine, aspartic acid, glutamic acid, lysine, omithine, histidine,arginine, cysteine, homocysteine, methionine, phenylalanine,homophenylalanine, phenylglycine, ortho-tyrosine, meta-tyrosine,para-tyrosine, tryptophan, glutamine, asparagine, proline andhydroxyproline. A “side chain of an α-amino acid” refers to the radicalfound on the α-carbon of an α-amino acid as defined above, for example,hydrogen (for glycine), methyl (for alanine), benzyl (forphenylalanine), and the like.

“Amino” refers to the group —NH₂. “Substituted amino,” refers to thegroup —NHR or —NRR where each R is independently selected from thegroup: optionally substituted alkyl, optionally substituted alkoxy,optionally substituted aryl, optionally substituted heterocyclyl, acyl,carboxy, alkoxycarbonyl, sulfanyl, sulfinyl and sulfonyl, e.g.,diethylamino, methylsulfonylamino, furanyl-oxy-sulfonamino.

“Aryl” refers to aromatic 6- to 14-membered carbocyclic rings include,e.g., benzene, naphthalene, indane, teralin, fluorene and the like.

“Arylene” refers to an “aryl” that is a linker between two other groups.For example, for G-V-B, “phenylene” for V refers to a benzene ringsystem that links G and B, that is, G and B are each attached todifferent carbons of V, leaving four potential sites for furthersubstitution on V.

“Arylalkyl” refers to a residue in which an aryl moiety is attached to aparent structure via one of an alkylene, alkylidene, or alkylidyneradical. Examples include benzyl, phenethyl, phenylvinyl, phenylallyland the like. The aryl, alkylene, alkylidene, or alkylidyne radicalportion of an arylalkyl group may be optionally substituted. “Lowerarylalkyl” refers to an arylalkyl where the “alkyl” portion of the grouphas one to eight carbons.

“Halogen” or “halo” refers to fluorine, chlorine, bromine or iodine.Dihaloaryl, dihaloalkyl, trihaloaryl etc. refer to aryl and alkylsubstituted with a plurality of halogens, but not necessarily aplurality of the same halogen; thus 4-chloro-3-fluorophenyl is withinthe scope of dihaloaryl.

“Heteroatom” refers to O, S, N, or P.

“Heterocyclyl” refers to a stable 3- to 15-membered ring radical thatconsists of carbon atoms and from one to five heteroatoms selected fromthe group consisting of nitrogen, phosphorus, oxygen and sulfur. Forpurposes of this invention, the heterocyclyl ring radical may be amonocyclic, bicyclic or tricyclic ring system, which may include fusedor bridged ring systems, either aromatic, saturated, or combinationsthereof; and the nitrogen, phosphorus, carbon or sulfur atoms in theheterocyclyl ring radical may be optionally oxidized to variousoxidation states, for example for the purposes of this invention and tonegate undo repetition in the description, the corresponding N-oxide ofpyridine derivatives, and the like, are understood to be included ascompounds of the invention. In addition, the nitrogen atom may beoptionally quaternized; and the ring radical may be partially or fullysaturated or aromatic. Examples of such heterocyclyl ring radicalsinclude, but are not limited to, azetidinyl, acridinyl, benzodioxolyl,benzodioxanyl, benzofuranyl, carbazoyl, cinnolinyl, dioxolanyl,indolizinyl, naphthyridinyl, perhydroazepinyl, phenazinyl,phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl,quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrazoyl,tetrahydroisoquinolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl,2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl,4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl,imidazolinyl, imidazolidinyl, dihydropyridinyl, tetrahydropyridinyl,pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolinyl,oxazolidinyl, triazolyl, indanyl, isoxazolyl, isoxazolidinyl,morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl, isothiazolyl,quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl,isoindolinyl, octahydroindolyl, octahydroisoindolyl, quinolyl,isoquinolyl, decahydroisoquinolyl, benzimidazolyl, thiadiazolyl,benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, tetrahydrofuryl,tetrahydropyranyl, thienyl, benzothieliyl, thiamorpholinyl,thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, dioxaphospholanyl,and oxadiazolyl.

“Heteroalicyclic” refers specifically to a non-aromatic heterocyclylring system radical. Heteroalicyclic ring systems include saturated andpartially bridged ring systems having geometries [4.4.0], [4.3.0],[4.2.0], [4.1.0], [3.3.0], [3.2.0], [3.1.0], [3.3.3], [3.3.2], [3.3.1],[3.2.2], [3.2.1], [2.2.2], [2.2.1], and the like.

“Heteroaryl” refers specifically to an aromatic heterocyclyl ring systemradical.

“Heteroarylene” refers to a “heteroaryl” that is a linker between twoother groups. For example, for M-P-L, “pyridylene” for P refers to apyridine ring system that links M and L, that is, M and L are eachattached to different atoms of P, leaving four potential sites forfurther substitution on P.

“Heterocyclylalkyl” refers to a residue in which a heterocyclyl ring isattached to a parent structure via one of an alkylene, alkylidene, oralkylidyne radical. Examples include (4-methylpiperazin-1-yl)methyl,(morpholin-4-yl)methyl, 2-(oxazolin-2-yl)ethyl,4-(4-methylpiperazin-1-yl)-2-butenyl, and the like. The heterocyclyl,alkylene, alkylidene, or alkylidyne radical portion of an arylalkylgroup may be optionally substituted. “Lower heterocyclylalkyl” refers toan arylalkyl where the “alkyl” portion of the group has one to eightcarbons.

The term “imino” refers to a substitution on a carbon atom, morespecifically to a doubly bonded nitrogen. For example, an imine, anamidine, and an oxime, all contain the “imino” group.

“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where said event or circumstance occurs and instances in whichit does not. It will be understood by those skilled in the art withrespect to any group containing one or more substituents that suchgroups are not intended to introduce any substitution or substitutionpatterns (e.g., substituted alkyl includes optionally substitutedcycloalkyl groups, which in turn are defined as including optionallysubstituted alkyl groups, potentially ad infinitum) that are stericallyimpractical and/or synthetically non-feasible. “Optionally substituted”refers to all subsequent modifiers in a term, for example in the term“optionally substituted C₁₋₈alkylaryl,” optional substitution may occuron both the “C₁₋₈alkyl” portion and the “aryl” portion of the molecule;and for example, optionally substituted alkyl includes optionallysubstituted cycloalkyl groups, which in turn are defined as includingoptionally substituted alkyl groups, potentially ad infinitum. If ahetercyclic ring is “optionally substituted,” then both the carbon andany heteroatoms in the ring may be substituted thereon. Examples ofoptional substitution include, but are not limited to alkyl, halogen,alkoxy, hydroxy, oxo, carbamyl, acylamino, sulfonamido, carboxy,alkoxycarbonyl, acyl, alkylthio, alkylsulfonyl, nitro, cyano, amino,alkylamino, cycloalkyl and the like. Thus, for example, if a group“—C(O)R” is described, where “R” is optionally substituted alkyl, then“R” would include, but not be limited to, —CH₂Ph, —CH₂CH₂OPh,—CH═CHPhCH₃, —C₃H₄CH₂N(H)Ph, and the like.

The term “ortho” is normally used in reference to relative position oftwo substituents on a benzene ring; however, in this application theterm “ortho” is meant to apply to other aromatic ring systems where twosubstituents reside on adjacent carbons. For example,3-bromo-4-fluoro-thiophene possesses a bromo group and a fluoro groupwhich have an ortho, or 1,2-positional relationship, to each other.

The term “oxo” refers to a substitution on a carbon atom, morespecifically to a doubly bonded oxygen. For example, an oxo-morpholine,a cyclohexanone, and an acyl group, all contain the “oxo” functionality.

“Saturated bridged ring system” refers to a bicyclic or polycyclic ringsystem that is not aromatic. Such a system may contain isolated orconjugated unsaturation, but not aromatic or heteroaromatic rings in itscore structure (but may have aromatic substitution thereon). Forexample, 2,3,3a,4,7,7a-hexahydro-1H-indene and1,2,3,4,4a,5,8,8a-octahydro-naphthalene are included in the class“saturated bridged ring system.”

“Substituted” alkyl, aryl, and heterocyclyl, refer respectively toalkyl, aryl, and heterocyclyl, wherein one or more (for example up toabout 5, in another example, up to about 3) hydrogen atoms are replacedby a substituent independently selected from the group: optionallysubstituted alkyl (e.g., fluoroalkyl), optionally substituted alkoxy,alkylenedioxy (e.g. methylenedioxy), optionally substituted amino (e.g.,alkylamino and dialkylamino), optionally substituted amidino, optionallysubstituted aryl (e.g., phenyl), optionally substituted arylalkyl (e.g.,benzyl), optionally substituted aryloxy (e.g., phenoxy), optionallysubstituted arylalkyloxy (e.g., benzyloxy), carboxy (—COOH), carboalkoxy(i.e., acyloxy or —OOCR), carboxyalkyl (i.e., esters or —COOR),carboxamido, aminocarbonyl, benzyloxycarbonylamino (CBZ-amino), cyano,carbonyl, halogen, hydroxy, optionally substituted heterocyclylalkyl,optionally substituted heterocyclyl, nitro, sulfanyl, sulfinyl,sulfonyl, and thio.

“Sulfanyl” refers to the groups: —S-(optionally substituted alkyl),—S-(optionally substituted aryl), and —S-(optionally substitutedheterocyclyl).

“Sulfinyl” refers to the groups: —S(O)—H, —S(O)-(optionally substitutedalkyl), —S(O)-optionally substituted aryl), and —S(O)-(optionallysubstituted heterocyclyl).

“Sulfonyl” refers to the groups: —S(O₂)—H, —S(O₂)-(optionallysubstituted alkyl), —S(O₂)-optionally substituted aryl),—S(O₂)-(optionally substituted heterocyclyl), —S(O₂)-(optionallysubstituted alkoxy), —S(O₂)-optionally substituted aryloxy), and—S(O₂)-(optionally substituted heterocyclyloxy).

The term “thiono” refers to a substitution on a carbon atom, morespecifically to a doubly bonded sulfur. For example, a thioketone and athioamide both contain the “thiono” functionality.

“Yield” for each of the reactions described herein is expressed as apercentage of the theoretical yield.

In some embodiments, as will be appreciated by those in the art, twoadjacent groups on an aromatic system may be fused together to form aring structure. The fused ring structure may contain heteroatoms and maybe optionally substituted with one or more groups. It shouldadditionally be noted that saturated carbons of such fused groups (i.e.saturated ring structures) may contain two substitution groups.

Some of the compounds of the invention may have imino, amino, oxo orhydroxy understood that such imino, amino, oxo or hydroxy substituentsmay exist in their corresponding tautomeric form, i.e., amino, imino,hydroxy or oxo, respectively. As well, tautomeric forms of ringconjugation, for example in a triazole, are understood to be within thescope of the invention, when formulae depict only one such tautomer.

Compounds of the invention are generally named using ACD/Name (availablefrom Advanced Chemistry Development, Inc. of Toronto, Canada). Thissoftware derives names from chemical structures according to systematicapplication of the nomenclature rules agreed upon by the InternationalUnion of Pure and Applied Chemistry (IUPAC), International Union ofBiochemistry and Molecular Biology (IUBMB), and the Chemical AbstractsService (CAS).

The compounds of the invention, or their pharmaceutically acceptablesalts, may have asymmetric carbon atoms, oxidized sulfur atoms orquaternized nitrogen atoms in their structure.

The compounds of the invention and their pharmaceutically acceptablesalts may exist as single stereoisomers, racemates, and as mixtures ofenantiomers and diastereomers. The compounds may also exist as geometricisomers. All such single stereoisomers, racemates and mixtures thereof,and geometric isomers are intended to be within the scope of thisinvention.

For linking groups, e.g. —OCH₂— or —C(═O)N(R)—, it is understood thateither of the linking groups two partners may be bound to either end ofthe linking group. Put another way, linking groups are understood todescribe both possible orientations between the A-OCH₂-B and A-CH₂O-Bare described. In the case of substituted linking groups, e.gsubstituted alkoxyl, it is assumed that the substitution is in additionto the two groups to which the linking group is attached.

Methods for the preparation and/or separation and isolation of singlestereoisomers from racemic mixtures or non-racemic mixtures ofstereoisomers are well known in the art. For example, optically active(R)- and (S)-isomers may be prepared using chiral synthons or chiralreagents, or resolved using conventional techniques. When desired, theR- and S-isomers may be resolved by methods known to those skilled inthe art, for example by: formation of diastereoisomeric salts orcomplexes which may be separated, for example, by crystallization; viaformation of diastereoisomeric derivatives which may be separated, forexample, by crystallization, gas-liquid or liquid chromatography;selective reaction of one enantiomer with an enantiomer specificreagent, for example enzymatic oxidation or reduction, followed byseparation of the modified and unmodified enantiomers; or gas-liquid orliquid chromatography in a chiral environment, for example on a chiralsupport, such as silica with a bound chiral ligand or in the presence ofa chiral solvent. It will be appreciated that where a desired enantiomeris converted into another chemical entity by one of the separationprocedures described above, a further step may be required to liberatethe desired enantiomeric form. Alternatively, specific enantiomer may besynthesized by asymmetric synthesis using optically active reagents,substrates, catalysts or solvents, or by converting on enantiomer to theother by asymmetric transformation. For a mixture of enantiomers,enriched in a particular enantiomer, the major component enantiomer maybe further enriched (with concomitant loss in yield) byrecrystallization.

The symbol “—” means a single bond, “═” means a double bond, “≡” means atriple bond, and “

” refers to a group on a double-bond as occupying either position on theterminus of a double bond to which the symbol is attached. When a groupis depicted removed from its parent formula, the “

” symbol will be used at the end of the bond which was theoreticallycleaved in order to separate the group from its parent structuralformula.

When a group “R” is depicted as existing on a ring system, as forexample in the formula

then a substituent “R” may reside on any atom of the ring system,assuming replacement of a depicted, implied, or expressly definedhydrogen from one of the ring atoms, so long as a stable structure isformed.

When a group “R” is depicted as existing on a fused ring system, as forexample in the formula

then a substituent “R” may reside on any atom of the fused ring system,assuming replacement of a depicted (e.g. the —NH— in the formula above),implied (e.g. as in the formula above, where the hydrogens are not shownbut understood to be present), or expressly defined hydrogen (e.g. wherein the formula above, “X” equals ═CH—) from one of the ring atoms, solong as a stable structure is formed. In the example depicted, the “R”group may reside on either the 5-membered or the 6-membered ring of thefused ring system. In the formula depicted above, when y is 2 forexample, then the two “R's” may reside on any two atoms of the ringsystem, again assuming each replaces a depicted, implied, or expresslydefined hydrogen on the ring. When there are more than one such depicted“floating” groups, as for example in the formula

where there are two groups, namely, the “R” and the bond indicatingattachment to a parent structure. In such cases, the “floating” groupsmay reside on any atoms of the ring system, again assuming each floatinggroup replaces a depicted, implied, or expressly defined unique hydrogenon the ring.

“Substituted cycloalkyl,” in this application, is meant to includebridged or fused ring systems wherein an all-carbon bridge portion ofsuch ring systems, along with the two bridgehead carbons, is consideredas a cycloalkyl. For example, the formula

depicts a bridged ring system that has “R” substitution and is itself asubstituent of a parent compound (as denoted by the

 symbol, supra). As mentioned above, either of the depicted “floating”groups may reside on either the alkyl bridge or the aromatic ring of thedepicted bridged ring system. In this application, for such ringsystems, when the parent compound is bonded to the alkyl bridge, as in

When a group “R” is depicted as existing on a saturated ring system, asfor example in the formula

where “y” can be more than one, assuming each replaces a currentlydepicted, implied, or expressly defined hydrogen on the ring, then wherethe resulting structure is stable, two “R's” may reside on the samecarbon. A simple example is when R is a methyl group, then in thisinstance there would exist a geminal dimethyl on a carbon of thedepicted ring. In another example, two R's on the same carbon, includingthat carbon, may form a ring, thus creating a spirocyclic ring structurewith the depicted ring.implied (e.g. as in the formula above, where the hydrogens are not shownbut understood to be present), or expressly defined hydrogen (e.g. wherein the formula above, “X” equals ═CH—) from one of the ring atoms, solong as a stable structure is formed. In the example depicted, the “R”group may reside on either the 5-membered or the 6-membered ring of thefused ring system. In the formula depicted above, when y is 2 forexample, then the two “R's” may reside on any two atoms of the ringsystem, again assuming each replaces a depicted, implied, or expresslydefined hydrogen on the ring. When there are more than one such depicted“floating” groups, as for example in the formula

where there are two groups, namely, the “R” and the bond indicatingattachment to a parent structure. In such cases, the “floating” groupsmay reside on any atoms of the ring system, again assuming each floatinggroup replaces a depicted, implied, or expressly defined unique hydrogenon the ring.

“Substituted cycloalkyl,” in this application, is meant to includebridged or fused ring systems wherein an all-carbon bridge portion ofsuch ring systems, along with the two bridgehead carbons, is consideredas a cycloalkyl. For example, the formula

depicts a bridged ring system that has “R” substitution and is itself asubstituent of a parent compound (as denoted by the

symbol, supra). As mentioned above, either of the depicted “floating”groups may reside on either the alkyl bridge or the aromatic ring of thedepicted bridged ring system. In this application, for such ringsystems, when the parent compound is bonded to the alkyl bridge, as in

When a group “R” is depicted as existing on a saturated ring system, asfor example in the formula

where “y” can be more than one, assuming each replaces a currentlydepicted, implied, or expressly defined hydrogen on the ring, then wherethe resulting structure is stable, two “R's” may reside on the samecarbon. A simple example is when R is a methyl group, then in thisinstance there would exist a geminal dimethyl on a carbon of thedepicted ring. In another example, two R's on the same carbon, includingthat carbon, may form a ring, thus creating a spirocyclic ring structurewith the depicted ring.

“Patient” for the purposes of the present invention includes humans andother animals, particularly mammals, and other organisms. Thus themethods are applicable to both human therapy and veterinaryapplications. In a preferred embodiment the patient is a mammal, and ina most preferred embodiment the patient is human.

“Kinase-dependent diseases or conditions” refer to pathologic conditionsthat depend on the activity of one or more protein kinases. Kinaseseither directly or indirectly participate in the signal transductionpathways of a variety of cellular activities including proliferation,adhesion, migration, differentiation and invasion.

While not wishing to be bound to theory, phosphatases can also play arole in “kinase-dependent diseases or conditions” as cognates ofkinases. That is, kinases phosphorylate and phosphates dephosphorylate,for example protein substrates. Therefore compounds of the invention,while modulating kinase activity as described herein, may also modulate,either directly or indirectly, phosphatase activity. This additionalmodulation, if present, may be synergistic (or not) to activity ofcompounds of the invention toward a related or otherwise interdependentkinase or kinase family. Thus, “kinase-dependent diseases or conditions”are those diseases that should be mitigated via treatment of a patientwith compounds and/or formulations of the invention. Kinase-dependentdiseases or conditions include diseases or disorders associated withuncontrolled, abnormal and/or unwanted cellular activities such as thoseset forth in paragraphs [0031]-[0038].

“Therapeutically effective amount” is an amount of a compound of theinvention, that when administered to a patient, ameliorates a symptom ofthe disease. The amount of a compound of the in which constitutes a“therapeutically effective amount” will vary depending on the compound,the disease state and its severity, the age of the patient to betreated, and the like. The therapeutically effective amount can bedetermined routinely by one of ordinary skill in the art having regardto his own knowledge and to this disclosure.

“Cancer” refers to cellular-proliferative disease states, including butnot limited to: Cardiac: sarcoma (angiosarcoma, fibrosarcoma,rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma andteratoma; Lung bronchogenic carcinoma (squamous cell, undifferentiatedsmall cell, undifferentiated large cell, adenocarcinoma), alveolar(bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma,chondromatous hanlartoma, inesothelioma; Gastrointestinal: esophagus(squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma),stomach (carcinoma, lymphoma, leiomyosarcoma, pancreas (ductaladenocarcinoma, insulinorna, glucagonoma, gastrinoma, carcinoid tumors,vipoma), small bowel (adenocarcinoma, lymphoma, carcinoid tumors,Karposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma,fibroma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma,hamartoma, leiomyoma); Genitourinary tract: kidney (adenocarcinoma,Wilm's tumor [neplrroblastoma], lymphoma, leukemia), bladder and urethra(squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma),prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma,embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma,interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors,lipoma); Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma,hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Bone:osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibroushistiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma(reticulum cell sarcoma), multiple myeloma, malignant giant cell tumorchordoma, osteochronfroma (osteocartilaginous exostoses), benignchondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma andgiant cell tumors; Nervous system: skull (osteoma, hemangioma,granuloma, xanthoma, osteitis defornians), meninges (meningioma,meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma,glioma, ependymoma, germinoma [pinealoma], glioblastoma multiform,oligodendroglioma, schwannoma, retinoblastoma, congenital tumors),spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecological:uterus (endometrial carcinoma), cervix (cervical carcinoma, pre-tumorcervical dysplasia), ovaries (ovarian carcinoma [serouscystadenocarcinoma, mucinous cystadenocarcinoma, unclassifiedcarcinoma], granulosa-thecal cell tumors, SertoliLeydig cell tumors,dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma,intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma),vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma(embryonal rhabdomyosarcoma], fallopian tubes (carcinoma); Hematologic:blood (myeloid leukemia [acute and chronic], acute lymphoblasticleukemia, chronic lymphocytic leukemia, myeloproliferative diseases,multiple myeloma, myelodysplastic syndrome), Hodgkin's disease,non-Hodgkin's lymphoma [malignant lymphoma]; Skin: malignant melanoma,basal cell carcinoma, squamous cell carcinoma, Karposi's sarcoma, molesdysplastic nevi, lipoma, angioma, dermatofibroma, keloids, psoriasis;and Adrenal lands: neuroblastoma. Thus, the term “cancerous cell” asprovided herein, includes a cell afflicted by any one of theabove-identified conditions.

“Pharmaceutically acceptable acid addition salt” refers to those saltsthat retain the undesirable, formed with inorganic acids such ashydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like, as well as organic acids such as aceticacid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid,oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid,tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid,methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid,salicylic acid and the like.

“Pharmaceutically acceptable base addition salts” include those derivedfrom inorganic bases such as sodium, potassium, lithium, ammonium,calcium, magnesium, iron, zinc, copper, manganese, aluminum salts andthe like. Exemplary salts are the ammonium, potassium, sodium, calcium,and magnesium salts. Salts derived from pharmaceutically acceptableorganic non-toxic bases include, but are not limited to, salts ofprimary, secondary, and tertiary amines, substituted amines includingnaturally occurring substituted amines, cyclic amines and basic ionexchange resins, such as isopropylamine, trimethylamine, diethylamine,triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol,2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine,caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine,glucosamine, methylglucamine, theobromine, purines, piperazine,piperidine, N-ethylpiperidine, polyamine resins, and the like. Exemplaryorganic bases are isopropylamine, diethylamine, ethanolamine,trimethylamine, dicyclohexylamine, choline, and caffeine. (See, forexample, S. M. Berge, et al., “Pharmaceutical Salts,” J. Pharm. Sci.,1977;66:1-19 which is incorporated herein by reference.)

“Prodrug” refers to compounds that are transformed (typically rapidly)in vivo to Common examples include, but are not limited to, ester andamide forms of a compound having an active form bearing a carboxylicacid moiety. Examples of pharmaceutically acceptable esters of thecompounds of this invention include, but are not limited to, alkylesters (for example with between about 1 and about 6 carbons) whereinthe alkyl group is a straight or branched chain. Acceptable esters alsoinclude cycloalkyl esters and arylalkyl esters such as, but not limitedto benzyl. Examples of pharmaceutically acceptable amides of thecompounds of this invention include, but are not limited to, primaryamides, and secondary and tertiary alkyl amides (for example withbetween about 1 and about 6 carbons). Amides and esters of the compoundsof the present invention may be prepared according to conventionalmethods. Another example of a prodrug is a pyridine group; in many casesthe pyridine group is oxidized to its corresponding N-oxide that may bea biologically active compound of the invention. Thus the “pyritlineform” may be thought of as a prodrug. A thorough discussion of prodrugsis provided in T. Higuchi and V. Stella, “Pro-drugs as Novel DeliverySystems,” Vol 14 of the A.C.S. Symposium Series, and in BioreversibleCarriers in Drug Design, ed. Edward B. Roche, American PharmaceuticalAssociation and Pergamon Press, 1987, both of which are incorporatedherein by reference.

“Metabolite” refers to the break-down or end product of a compound orits salt produced by metabolism or biotransformation in the animal orhuman body; e.g., biotransformation to a more polar molecule such as byoxidation, reduction, or hydrolysis, or to a conjugate (see Goodman andGilman, “The Pharmacological Basis of Therapeutics” 8.sup.th Ed.,Pergamon Press, Gilman et al. (eds), 1990 for a discussion ofbiotransformation). As used herein, the metabolite of a compound of theinvention or its salt may be the biologically active form of thecompound in the body. In one example, a prodrug may be used such thatthe biologically active form, a metabolite, is released in vivo. Inanother example, a biologically active metabolite is discoveredserendipitously, that is, no prodrug design per se was undertaken. Anassay for activity of a metabolite of a compound of the presentinvention is known to one of skill in the art in light of the presentdisclosure.

In addition, the compounds of the present invention can exist inunsolvated as well as solvated forms with pharmaceutically acceptablesolvents such as water, ethanol, and the like. In general, the solvatedforms are considered equivalent to the unsolvated forms for the purposesof the present invention.

In addition, it is intended that the present invention cover compoundsmade either using standard organic synthetic techniques, includingcombinatorial chemistry or by biological methods, such as bacterialdigestion, metabolism, enzymatic conversion, and the like.

“Treating” or “treatment” as used herein covers the treatment of adisease-state in a human, which disease-state is characterized byuncontrolled, abnormal or unwanted cellular proliferation,differentiation, programmed cell death migration or chemoinvasion andinvasion and includes at least one of: (i) preventing the disease-statefrom occurring in a human, in particular, when such human is predisposedto the disease-state but has not yet been diagnosed as having it; (ii)inhibiting the disease-state, i.e., arresting its development; and (iii)relieving the disease-state, i.e., causing regression of thedisease-state. As is known in the art, adjustments for systemic versuslocalized delivery, age, body weight, general health, sex, diet, time ofadministration, drug interaction and the severity of the condition maybe necessary, and will be ascertainable with routine

General Administration

Administration of the compounds of the invention, or theirpharmaceutically acceptable salts, in pure form or in an appropriatepharmaceutical composition, can be carried out via any of the acceptedmodes of administration or agents for serving similar utilities. Thus,administration can be, for example, orally, nasally, parenterally(intravenous, intramuscular, or subcutaneous), topically, transdermally,intravaginally, intravesically, intracistemally, or rectally, in theform of solid, semi-solid, lyophilized powder, or liquid dosage forms,such as for example, tablets, suppositories, pills, soft elastic andhard gelatin capsules, powders, solutions, suspensions, or aerosols, orthe like, preferably in unit dosage forms suitable for simpleadministration of precise dosages.

The compositions will include a conventional pharmaceutical carrier orexcipient and a compound of the invention as the/an active agent, and,in addition, may include other medicinal agents, pharmaceutical agents,carriers, adjuvants, etc. Compositions of the invention may be used incombination with anticancer or other agents that are generallyadministered to a patient being treated for cancer. Adjuvants includepreserving, wetting, suspending, sweetening, flavoring, perfuming,emulsifying, and dispensing agents. Prevention of the action ofmicroorganisms can be ensured by various antibacterial and antifungalagents, for example, parabens, chlorobutanol, phenol, sorbic acid, andthe like. It may also be desirable to include isotonic agents, forexample sugars, sodium chloride, and the like. Prolonged absorption ofthe injectable pharmaceutical form can be brought about by the use ofagents delaying absorption, for example, aluminum monostearate andgelatin.

If desired, a pharmaceutical composition of the invention may alsocontain minor amounts of auxiliary substances such as wetting oremulsifying agents, pH buffering agents, antioxidants, and the like,such as, for example, citric acid, sorbitan monolaurate, triethanolamineoleate, butylalted hydroxytoluene, etc.

Compositions suitable for parenteral injection may comprisephysiologically acceptable sterile aqueous or nonaqueous solutions,dispersions, suspensions or emulsions, and sterile powders forreconstitution into sterile injectable solutions or dispersions.Examples of suitable aqueous and nonaqueous carriers, diluents, solventsor vehicles include water, ethanol, polyols (propyleneglycol,polyethyleneglycol, glycerol, and the like), suitable mixtures thereof,vegetable oils (such as olive oil) and injectable organic esters such asethyl oleate. Proper fluidity can be maintained, for example, by the useof a coating such as lecithin, by the maintenance of the requiredparticle size in the case of dispersions and by the use of surfactants.

One preferable route of administration is oral, using a convenient dailydosage regimen that can be adjusted according to the degree of severityof the disease-state to be treated.

Solid dosage forms for oral administration include capsules, tablets,pills, powders, and granules. In such solid dosage forms, the activecompound is admixed with at least one inert customary excipient (orcarrier) such as sodium citrate or dicalcium phosphate or (a) fillers orextenders, as for example, starches, lactose, sucrose, glucose,mannitol, gelatin, polyvinylpyrrolidone, sucrose, and gum acacia, (c)humectants, as for example, glycerol, (d) disintegrating agents, as forexample, agar-agar, calcium carbonate, potato or tapioca starch, alginicacid, croscarmellose sodium, complex silicates, and sodium carbonate,(e) solution retarders, as for example paraffin, (f) absorptionaccelerators, as for example, quaternary ammonium compounds, (g) wettingagents, as for example, cetyl alcohol, and glycerol monostearate,magnesium stearate and the like (h) adsorbents, as for example, kaolinand bentonite, and (i) lubricants, as for example, talc, calciumstearate, magnesium stearate, solid polyethylene glycols, sodium laurylsulfate, or mixtures thereof. In the case of capsules, tablets, andpills, the dosage forms may also comprise buffering agents.

Solid dosage forms as described above can be prepared with coatings andshells, such as enteric coatings and others well known in the art. Theymay contain pacifying agents, and can also be of such composition thatthey release the active compound or compounds in a certain part of theintestinal tract in a delayed manner. Examples of embedded compositionsthat can be used are polymeric substances and waxes. The activecompounds can also be in microencapsulated form, if appropriate, withone or more of the above-mentioned excipients.

Liquid dosage forms for oral administration include pharmaceuticallyacceptable emulsions, solutions, suspensions, syrups, and elixirs. Suchdosage forms are prepared, for example, by dissolving, dispersing, etc.,a compound(s) of the invention, or a pharmaceutically acceptable saltthereof, and optional pharmaceutical adjuvants in a carrier, such as,for example, water, saline, aqueous dextrose, glycerol, ethanol and thelike; solubilizing agents and emulsifiers, as for example, ethylalcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzylalcohol, benzyl benzoate, propyleneglycol, 1,3-butyleneglycol,dimethylformamide; oils, in particular, cottonseed oil, groundnut oil,corn germ oil, olive oil, castor oil and sesame oil, glycerol,tetrahydrofurfuryl alcohol, polyethyleneglycols and fatty acid esters ofsorbitan; or mixtures of these substances, and the like, to thereby forma solution or suspension.

Suspensions, in addition to the active compounds, may contain suspendingagents, as for example, ethoxylated isostearyl alcohols, polyoxyethylenesorbitol and sorbitan esters, microcrystalline cellulose, aluminummetahydroxide, bentonite, agar-agar and tragacanth, or mixtures of thesesubstances, and the like.

Compositions for rectal administrations are, for example, suppositoriesthat can be prepared by mixing the compounds of the present inventionwith for example suitable non-irritating excipients or carriers such ascocoa butter, polyethyleneglycol or a suppository wax, which are solidat ordinary temperatures but liquid at body temperature and therefore,melt while in a suitable body cavity and release the active componenttherein.

Dosage forms for topical administration of a compound of this inventioninclude ointments, powders, sprays, and inhalants. The active componentis admixed under sterile conditions with a physiologically acceptablecarrier and any preservatives, buffers, or propellants as may berequired. Ophthalmic formulations, eye ointments, powders, and solutionsare also contemplated as being within the scope of this invention.

Generally, depending on the intended mode of administration, thepharmaceutically acceptable compositions will contain about 1% to about99% by weight of a compound(s) of the invention, or a pharmaceuticallyacceptable salt thereof, and 99% to 1% by weight of a suitablepharmaceutical excipient. In one example, the composition will bebetween about 5% and about 75% by weight of a compound(s) of theinvention, or a pharmaceutically acceptable salt thereof, with the restbeing suitable pharmaceutical excipients.

Actual methods of preparing such dosage forms are known, or will beapparent, to those skilled in this art; for example, see Remington'sPharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton,Pa., 1990). The composition to be administered will, in any event,contain a therapeutically effective amount of a compound of theinvention, or a pharmaceutically acceptable salt thereof, for treatmentof a disease-state in accordance with the teachings of this invention.

The compounds of the invention, or their pharmaceutically acceptablesalts, are administered in a therapeutically effective amount which willvary depending upon a variety of factors including the activity of thespecific compound employed, the metabolic stability and length of actionof the compound, the age, body weight, general health, sex, diet, modeand time of administration, rate of excretion, drug combination, theseverity of the particular disease-states, and the host undergoingtherapy. The compounds of the present invention can be administered to apatient at dosage levels in the range of about 0.1 to about 1,000 mg perday. For a normal human adult having a body weight of about 70kilograms, a dosage in the range of about 0.01 to about 100 mg perkilogram of body weight per day is an example. The specific dosage used,however, can vary. For example, the dosage can depend on a number offactors including the requirements of the patient, the severity of thecondition being treated, and the pharmacological activity of thecompound being used. The determination of optimum dosages for aparticular patient is well known to those skilled in the art.

Utility of Compounds of the Invention as Screening Agents

To employ the compounds of the invention in a method of screening forcandidate agents that bind to, for example a Chk1 receptor kinase, theprotein is bound to a support, and a compound of the invention is addedto the assay. Alternatively, the compound of the invention is bound tothe support and the protein is added. Classes of candidate agents amongwhich novel binding agents may be sought include specific antibodies,non-natural binding agents identified in screens of chemical libraries,peptide analogs, etc. Of particular interest are screening assays forcandidate agents that have a low toxicity for human cells. A widevariety of assays may be used for this purpose, including labeled invitro protein-protein binding assays, electrophoretic mobility shiftassays, immunoassays for protein binding, functional assays(phosphorylation assays, etc.) and the like.

The determination of the binding of the candidate agent to, for example,a Chk1 protein may be done in a number of ways. In one example, thecandidate agent (the compound of the invention) is labeled, for example,with a fluorescent or radioactive moiety and binding determineddirectly. For example, thus may be done by attaching all or a portion ofthe Chk1 protein to a solid support, adding a labeled agent (for examplea compound of the invention in which at least one atom has been replacedby a detectable isotope), washing off excess reagent, and determiningwhether the amount of the label is that present on the solid support.Various blocking and washing steps may be utilized as is known in theart.

By “labeled” herein is meant that the compound is either directly orindirectly labeled with a label which provides a detectable signal,e.g., radioisotope, fluorescent tag, enzyme, antibodies, particles suchas magnetic particles, chemiluminescent tag, or specific bindingmolecules, etc. Specific binding molecules include pairs, such as biotinand streptavidin, digoxin and antidigoxin etc. For the specific bindingmembers, the complementary member would normally be labeled with amolecule which provides for detection, in accordance with knownprocedures, as outlined above. The label can directly or indirectlyprovide a detectable signal.

In some embodiments, only one of the components is labeled. For example,a Chk1 protein may be labeled at tyrosine positions using ¹²⁵I, or withfluorophores. Alternatively, more than one component may be labeled withdifferent labels; using ¹²⁵I for the proteins, for example, and afluorophor for the candidate agents.

The compounds of the invention may also be used as competitors to screenfor additional drug candidates. “Candidate bioactive agent” or “drugcandidate” or grammatical equivalents as used herein describe anymolecule, e.g., protein, oligopeptide, small organic molecule,polysaccharide, polynucleotide, etc., to be tested for bioactivity. Theymay be capable of directly or indirectly altering the cellularproliferation phenotype or the expression of a cellular proliferationsequence, including both nucleic acid sequences and protein sequences.In other cases, alteration of cellular proliferation protein bindingand/or activity is screened. In the case where protein binding oractivity is screened, some embodiments exclude molecules already knownto bind to that particular protein. Exemplary embodiments of assaysdescribed herein include candidate agents, which do not bind the targetprotein in its endogenous native state, termed herein as “exogenous”agents. In one example, exogenous agents further exclude antibodies toChk1.

Candidate agents can encompass numerous chemical classes, thoughtypically they are organic molecules having a molecular weight of morethan about 100 and less than about 2,500 daltons. Candidate agentscomprise functional groups necessary for structural interaction withproteins, particularly hydrogen bonding and lipophilic binding, andtypically include at least an amine, carbonyl, hydroxyl, ether, orcarboxyl group, for example at least two of the functional chemicalgroups. The candidate agents often comprise cyclical carbon orheterocyclyl structures and/or aromatic or polyaromatic structuressubstituted with one or more of the above functional groups. Candidateagents are also found among biomolecules including peptides,saccharides, fatty acids, steroids, purines, pyrimidines, derivatives,structural analogs, or combinations thereof.

Candidate agents are obtained from a wide variety of sources includinglibraries of synthetic or natural compounds. For example, numerous meansare available for random and directed synthesis of a wide variety oforganic compounds and biomolecules, including expression of randomizedoligonucleotides. Alternatively, libraries of natural compounds in theform of bacterial, fungal, plant and animal extracts are available orreadily produced. Additionally, natural or synthetically producedlibraries and compounds are readily modified through conventionalchemical, physical and biochemical means. Known pharmacological agentsmay be subjected to directed or random chemical modifications, such asacylation, alkylation, esterification, amidification to producestructural analogs.

In one example, the binding of the candidate agent is determined throughthe use of competitive binding assays. In this example, the competitoris a binding moiety known to bind to Chk1, such as an antibody, peptide,binding partner, ligand, etc. Under certain circumstances, there may becompetitive binding as between the candidate agent and the bindingmoiety, with the binding moiety displacing the candidate agent.

In some embodiments, the candidate agent is labeled. Either thecandidate agent, or the competitor, or both, is added first to Chk1 fora time sufficient to allow binding, if present. Incubations may beperformed at any temperature that facilitates optimal activity,typically between 4° C. and 40° C.

Incubation periods are selected for optimum activity, but may also beoptimized to facilitate rapid high throughput screening. Typicallybetween 0.1 and 1 hour will be sufficient. Excess reagent is generallyremoved or washed away. The second component is then added, and thepresence or absence of the labeled component is followed, to indicatebinding.

In one example, the competitor is added first, followed by the candidateagent. Displacement of the competitor is an indication the candidateagent is binding to Chk1 and thus is capable of binding to, andpotentially modulating, the activity of the Chk1. In this embodiment,either component can be labeled. Thus, for example, if the competitor islabeled, the presence of label in the wash solution indicatesdisplacement by the agent. Alternatively, if the candidate agent islabeled, the presence of the label on the support indicatesdisplacement.

In an alternative embodiment, the candidate agent is added first, withincubation and washing, followed by the competitor. The absence ofbinding by the competitor may indicate the candidate agent is bound toChk1 with a higher affinity. Thus, if the candidate agent is labeled,the presence of the label on the support, coupled with a lack ofcompetitor binding, may indicate the candidate agent is capable ofbinding to Chk1.

It may be of value to identify the binding site of Chk1. This can bedone in a variety of ways. In one embodiment, once Chk1 has beenidentified as binding to the candidate agent, the Chk1 is fragmented ormodified and the assays repeated to identify the necessary componentsfor binding.

Modulation is tested by screening for candidate agents capable ofmodulating the activity of Chk1 comprising the steps of combining acandidate agent with Chk1, as above, and determining an alteration inthe biological activity of the Chk1. Thus, in this embodiment, thecandidate agent should both bind to (although this may not benecessary), and alter its biological or biochemical activity as definedherein. The methods include both in vitro screening methods and in vivoscreening of cells for alterations in cell viability, morphorlogy, andthe like.

Alternatively, differential screening may be used to identify drugcandidates that bind to native Chk1, but cannot bind to modified Chk1.

Positive controls and negative controls may be used in the assays. Forexample, all control and test samples are performed in at leasttriplicate to obtain statistically significant results. Incubation ofsamples is for a time sufficient for the binding of the agent to theprotein. Following incubation, samples are washed free ofnon-specifically bound material and the amount of bound, generallylabeled agent determined. For example, where a radiolabel is employed,the samples may be counted in a scintillation counter to determine theamount of bound compound.

A variety of other reagents may be included in the screening assays.These include reagents like salts, neutral proteins, e.g., albumin,detergents, etc which may be used to facilitate optimal protein-proteinbinding and/or reduce non-specific or background interactions. Alsoreagents that otherwise improve the efficiency of the assay, such asprotease inhibitors, nuclease inhibitors, anti-microbial agents, etc.,may be used. The mixture of components may be added in any order thatprovides for the requisite binding.

Abbreviations and Their Definitions

The following abbreviations and terms have the indicated meaningsthroughout:

-   -   Ac=acetyl    -   ATP=adenosine triphosphate    -   Boc=t-butyloxy carbonyl    -   br=broad    -   Bu=butyl    -   C=degrees Celsius    -   c-=cyclo    -   CBZ=carbobenzoxy=benzyloxycarbonyl    -   d=doublet    -   dd=doublet of doublet    -   dt=doublet of triplet    -   DBU=diazabicyclo[5.4.0]undec-7-ere    -   DCM=dichloromethane=methylene chloride=CH₂Cl₂    -   DCE=dichloroethylene    -   DEAD=diethyl azodicarboxylate    -   DIC=diisopropylcarbodiimide    -   DIEA=N,N-diisopropylethyl amine    -   DMAP=4-N,N-dimethylaminopyridine    -   DMF=N,N-dimethylfonnamide    -   DMSO=dimethyl sulfoxide    -   DVB=1,4-divinylbenzene    -   EEDQ=2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline    -   EI=Electron Impact ionization    -   Et=ethyl    -   Fmoc=9-fluorenylmethoxycarbonyl    -   g=gram(s)    -   GC=gas chromatography    -   h or hr=hour(s)    -   HATU=0-(7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium        hexafluorophosphate    -   HMDS=hexamethyldisilazane    -   HOAc=acetic acid    -   HOBt=hydroxybenzotriazole    -   HPLC=high pressure liquid chromatography    -   L=liter(s)    -   M=molar or molarity    -   m=multiplet    -   Me=methyl    -   mesyl=methanesulfonyl    -   mg=milligram(s)    -   MHz=megahertz (frequency)    -   min=minute(s)    -   mL=milliliter(s)    -   mM=millimolar    -   mmol=millimole(s)    -   mol=mole(s)    -   MS=mass spectral analysis    -   MTBE=methyl t-butyl ether    -   N=normal or normality    -   NBS=N-bromosuccinimide    -   NCS=N-chlorosuccinimide    -   nM=nanomolar    -   NMO=N-methylmorpholine oxide    -   NMR=nuclear magnetic resonance spectroscopy    -   PEG=polyethylene glycol    -   pEY=poly-glutamine, tyrosine    -   Ph=phenyl    -   PhOH=phenol    -   PfP=pentafluorophenol    -   PfPy=pentafluoropyridine    -   PPTS=pyridinium p-toluenesulfonate    -   PyBroP=bromo-tris-pyrrolidino-phosphonium hexafluorophosphate    -   q=quartet    -   RT=room temperature    -   Sat'd=saturated    -   s=singlet    -   s-=secondary    -   t-=tertiary    -   t or tr=triplet    -   TBDMS=t-butyldimethylsilyl    -   TES=triethylsilane    -   TFA=trifluoroacetic acid    -   TMOF=trimethyl orthoformate    -   TMS=trimethylsilyl    -   tosyl=p-toluenesulfonyl    -   Trt=triphenylmethyl    -   uL=microliter(s)    -   uM=micromole(s) or micromolar        Synthesis of Compounds

Scheme 1 depicts general synthetic routes for compounds of the inventionand is not intended to be limiting. Specific examples are describedsubsequently to these general synthetic descriptions. In thegeneralizations below, specific reaction conditions, for example,reagents such as added bases, acids, solvents, temperature, and the likeare not described so as not to confuse the discussion.

The general routes, in conjunction with the specific examples, containsufficient information to allow one skilled in the art to synthesizecompounds of the invention. In Scheme 1, some substituents are notdefined described as taking part in the synthesis of compounds of theinvention. This is done purely for simplification of description ofsyntheses. Such substituents in formula I may be appended to thescaffold of formula I at any time during synthesis or may pre-exist onintermediates or starting materials used to make compounds of theinvention, as would be understood by one skilled in the art. Morespecific examples are presented below to more fully describe theinvention.

Scheme 1 depicts examples of how compounds of the invention, consistentwith formula I, are made (in these examples for simplicity ofdiscussion, substituents R¹, R², and R³ are —H, but this is not alwaysthe case). Generally, but not necessarily, a starting material will takethe form of, for example, (i) or (ii). For example, (i) may take theform of a commercially available 3-amino-pyrazine (where Z is N). Thegroup “F₁” represents functionality that can be converted to, orfunctionality that exists in, compounds of formula I. For example if F₁represents a carboxylic acid group, then where A, of formula I, is acarbonyl, then (ii) may more appropriately represent the startingmaterial. In other cases, A is introduced into (i) to make (ii). Forexample, if F₁ is a cyano group, then in some instances the cyano groupin (i) is converted to a triazole ring system to produce A in (ii).

F₂ represents a functionality that is ultimately converted to, or usedin the production or introduction of, E of formula I. For example, if F₁is a carboxylic acid, then -A-F₂ can represent the esterified form ofthe carboxylic acid. If F₁ is a cyano group, then -A-F₂ can represent,for example, a triazole ring with appended functionality for subsequenttransformation. Although not depicted, the functionality -A-E may existin commercially available starting materials, or be introduced in asingle step to (i).

F₃ represents a functionality that is ultimately converted to, or usedin the production or introduction of, W of formula I. For example,intermediate (ii) is brominated selectively to afford (iii) where F₃ is—Br. Using aryl-aryl coupling reactions known to one skilled in the art,W is introduced, preferably with functionality F₄, into (iii) to makeintermediate (v). F₄ represents a functionality that is ultimatelyconverted to, or used in the production or introduction of, X of formulaI. Alternatively, (iii) is converted to (iv) via introduction of E (forexample an ester represented by -A-F₂ is converted to an amiderepresented by -A-E). Scheme 1 depicts only a subset of possiblevariations of making compounds of the invention.

Still referring to Scheme 1, intermediate (v) can be converted tointermediate (vi) via introduction of E (intermediate (vi) can also bemade from (iv) via introduction of −W—F₄). Also from intermediate (v), Xis introduced, preferably with functionality F₅, to make intermediate(vii). F₅ represents a functionality that is ultimately converted to, orused in the production or introduction of, Y of formula I. In manyexamples, —X—F₅ represents a linking group X with a reactivefunctionality, F₅, that is used to attach Y to X. In such cases, (vii)is converted to (ix). Alternatively, intermediate (vii) is converted,via introduction of —X—F₅, into (viii). Compounds of formula (x) aremade from either intermediate (ix) or (viii). Compounds (x) areconsistent with, and a subset of, formula I of the invention.

Thus compounds of the invention are generally made as depicted inScheme 1. One skilled in the art would recognize that many variations ofsynthetic routes not included in Scheme 1 are possible, and thus arewithin the scope of the invention.

Scheme 2 depicts a general method of making3-amino-pyrazine-2-carboxamides of the invention. Commercially availablemethyl 3-amino-pyrazine-2-carboxylate was brominated using the procedureof Russ, T., Ried, W., Ullrich, F., and Mutschler, E. Arch. Pharm.(Weinheim) 1992, 375, 761-767 (by analogy, bromination of commerciallyavailable 2-aminonicotinic acid (for example as described in U.S. Pat.Nos. 3,950,160, and 4,361,700) affords2-amino-5-bromopyridine-3-carboxylic acid. This intermediate can be usedto make corresponding amino-pyridine analogues using similar methodssimilar to those described in Schemes 1-4 for 3-amino-pyrazinecompounds.) The resulting bromo ester, (xi), was utilized, for example,in a Suzuki coupling with arylboronic acids by the method of W. J.Thompson, J. H. Jones, P. A. Lyle, and J. E. Thies J. Org. Chem. 1988,53, 2052-2055 or a similar procedure. The resulting aryl substitutedpyrazine ester, (xiv), was then hydrolyzed to the corresponding acid(xv). Acid (xv) was coupled with primary and secondary amines to giveamides, (xvi), followed by removal of any protecting groups ifnecessary. Alternatively, aryl substituted pyrazine ester (xiv) wasreacted directly with ammonia, methylamine, or other amines in asuitable solvent at elevated temperatures to afford amides (xvi). Againalternatively, bromopyrazine ester (xi) was converted (typically viahydrolysis) to bromopyrazine acid (xii), which was then coupled withamines to afford amides (xiii). The resulting bromo-pyrazine amides(xiii) were then, for example, coupled with arylboronic acids underSuzuki conditions to afford amides (xvi). In amides (xvi), the group—NR_(a)R_(b) represents -E of formula I.

Alternatively, the ester moiety for example in intermediates (xi) and(xiv) were converted to an acid, amide, nitrile, aldehyde,hydroxymethyl, or other functional groups. These functional groups werethen be elaborated into oximes, imines, hydrazones, or heterocycles suchas triazoles, pyrimidines, oxadiazoles, and other heterocycles inaccordance with group -A-E of formula I. More detailed descriptions ofexemplary transformations are described below.

Typically, but not necessarily, the aryl groups (denoted Ar in Scheme 2,corresponding to W in formula I) contained functional groups such as anester, aldehyde, hydroxymethyl, amine, hydroxyl, or other groups thatwere modified or functionalized either before or after the the arylgroups were coupled to, for example the bromo pyrazine. Schemes 3 and 4depict a number of typical transformations that were carried out to formgroup —X—Y onto W, in cases where W was a meta-phenylene. These arepresented as examples and are not intended to limit the scope of theinvention.

Referring to Scheme 3, benzylic amine intermediate (xix) was formed, forexample, either from benzylic alcohol intermediate (xvii) or arylaldehyde intermediate (xviii) using standard synthetic techniques. Forexample, the —OH group of (xvii) was transformed into a leaving groupand subsequently displaced with ammonia or an ammonia equivalent (suchas a phthalimide) to form (xix). Alternatively, aldehyde (xviii)acylated, for example with acid chlorides, to form (xx) (according toformula I, W is meta-phenylene and X is —C(═O)NHCH₂—). Intermediate(xix) in many cases was, or otherwise could be, also reacted withsulfonyl chlorides, isocyanates, and other electrophiles. In anotherexample, intermediate (xix) was subjected to reductive aminationconditions to provide compounds (xxi).

Scheme 4 shows additional transformations that were carried out to formgroup —X—Y onto W, in cases where W was a meta-phenylene. For example:esters (xxii) were converted to amides (xxiii), phenols (xxiv) wereconverted to ethers (xxv), and anilines (xxvi) were converted to amides(xxvii).

EXAMPLES

The following examples serve to more fully describe the manner of usingthe above-described invention, as well as to set forth the best modescontemplated for carrying out various aspects of the invention. It isunderstood that these examples in no way serve to limit the true scopeof this invention, but rather are presented for illustrative purposes.All references cited herein are incorporated by reference in theirentirety. Generally, but not necessarily, each example set out belowdescribes a multi-step synthesis as outlined above.

Example 1

3-amino-6-phenyl-N-(phenylmethyl)pyrazine-2-carboxamide

Methyl 3-amino-6-bromo-pyrazine-2-carboxylate: Commercially availablemethyl 3-amino-pyrazine-2-carboxylate (available from Aldrich ChemicalCompany) was brominated using a procedure similar to that of Russ, T.,Ried, W., Ullrich, F., and Mutschler, E. Arch. Pharm. (Weinheim) 1992,325, 761-767. To a solution of methyl 3-amino-2-pyrazine carboxylate(30.0 g, 200 mmol) in acetic acid (200 mL), bromine (11 mL) was addedslowly via addition funnel. After complete addition of bromine, sodiumcarbonate powder was added slowly until precipitation occurred. Thereaction mixture was allowed to stir at room temperature for 2 h. Thereaction mixture was reduced to half-volume in vacuo and then dilutedwith water (500 mL). The reaction mixture was shaken vigorously and theresulting solid was collected using vacuum filtration. The solid waswashed with ether to afford a pure yellow solid (91% yield).

Methyl 3-amino-6-phenylpyrazine-2-carboxylate: Methyl3-amino-6-phenylpyrazine-2-carboxylate was prepared from methyl3-amino-6-bromo-pyrazine-2-carboxylate using the procedure similar tothat of W. J. Thompson, J. H. Jones, P. A. Lyle, and J. E. Thies J. Org.Chem. 1988, 53, 2052-2055.

3-amino-6-phenylpyrazine-2-carboxylic acid: To a solution of methyl3-amino-6-phenylpyrazine-2-carboxylate (1.2 g, 5.26 mmol) in methanol (5mL) was added 6.0 N aqueous sodium hydroxide (6 mL) at room temperature.The solution was stirred at 50 C. for 3 h. The reaction was neutralizedslowly by adding 2.0 N hydrochloric acid until the pH of the solutionbecame in the 2-3 range at 0° C. The solution was extracted with ethylacetate (50 mL). The organic layer was washed with saturated aqueoussodium chloride (50 mL) and dried over magnesium sulfate. Filtration andconcentration at reduced pressure afforded3-amino-6-phenylpyrazine-2-carboxylic acid (0.59 g, 52% yield): MS (EI)for C₁₁H₉O₂: 216 (MH⁺)

3-amino-6-phenyl-N-(phenylmethyl)pyrazine-2-carboxamide: To a solutionof 3-amino-6-phenylpyrazine carboxylic acid (0.10 g, 0.47 mmol) indichloromethane (3 mL) were added1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 0.11 g,0.56 mmol), 1-hydroxybenzotriazole (HOBT, 75 mg, 0.56 mmol), andN-methylmorpholine (NMM, 56 mg, 0.56 mmol) at room temperature. Thereaction was stirred for 15 min before benzylamine (0.56 mmol) wasadded. The reaction mixture was allowed to stir overnight. The reactionwas diluted with ethyl acetate (200 mL) and washed with water (50 mL),saturated aqueous sodium bicarbonate (40 mL) and aqueous hydrochloricacid (30 mL), and saturated aqueous sodium chloride (25 mL). The organiclayer was dried over magnesium sulfate, filtered and concentrated atreduced pressure to afford product (91 mg, 67% yield) as light yellowsolid: ¹H NMR (400 MHz, CDCl₃): δ 8.62 (s, 1H), 8.38 (br s, 1H), 7.84(dd, 2H), 7.45 (m, 2H), 7.38 (m, 6H), 4.70 (d, 2H); MS (EI) forC₁₈H₁₆N₄O: 305 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-N,6-diphenylpyrazine-2-carboxamide: ¹H NMR (400 MHz, CDCl₃):9.92 (br s, 1H), 8.70 (s, 1H), 7.90 (dd, 2H), 7.72 (dd, 2H), 7.52 (m,2H), 7.46 (m, 3H), 7.20 (t, 1H); MS (EI) for C₁₇H₁₄N₄O: 290(MH⁺).

5-phenyl-3-(pyrrolidin-1-ylcarbonyl)pyrazin-2-amine: ¹H NMR (400 MHz,CDCl₃): δ 8.58 (s, 1H), 7.82(d, 2H), 7.45 (t, 2H), 7.40 (m, 1H), 6.40(br s, 2H), 4.02 (m,1H), 4.70(m, 1H), 2.04 (m, 4H); MS (EI) forC₁₅H₁₆N₄O: 269 (MH⁺).

3-amino-N-(cyclopropylmethyl)-6-phenylpyrazine-2-carboxamide: ¹H NMR(400 MHz, CDCl₃): δ 8.62 (s, 1H), 8.10 (br s, 1H), 7.85 (dd, 2H), 7.50(t, 2H), 7.40 (m, 1H), 3.30 (m, 2H), 1.10 (m, 1H), 0.80 (m, 2H), 0.30(m, 2H); MS (EI) for C₁₅H₁₆N₄O: 269 (MH⁺).

3-amino-6-phenyl-N-(tetrahydrofuran-2-ylmethyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): δ 8.60 (s, 1H), 8.30 (br s, 1H), 7.84 (d, 2H),7.50 (t, 2H), 7.40 (m, 1H), 4.10 (m, 1H), 3.94 (m, 1H), 3.80 (m, 1H),3.70 (m, 1H), 3.45 (m, 1H), 2.01 (m, 3H), 1.62 (m, 1H); MS (EI) forC₁₆H₁₈N₄O₂: 299 (MH⁺).

3-amino-N-cyclohexyl-6-phenylpyrazine-2-carboxamide: ¹H NMR (400 MHz,CDCl₃): δ 8.80 (s, 1H), 7.92 (br s, 1H), 7.82 (d, 2H), 7.45 (t, 2H),7.40 (m, 2H), 3.90 (m, 1H), 2.01 (m, 2H), 1.90 (m, 2H), 1.85(m, 1H),1.40 (m, 5H); MS (EI) for C₁₇H₂₀N₄O: 297 (MH⁺).

3-amino-6-phenyl-N-(2-phenylethyl)pyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.82 (m, 2H), 8.06 (m, 2H), 7.65 (br s, 2H), 7.49-7.20(m, 8H), 3.58 (t, 2H), 2.90 (t, 2H); MS (EI) for C₁₉H₁₈N₄: 319.2 (MH⁺).

3-amino-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-6-phenylpyrazine-2-carboxamide:MS (EI) for C₂₀H₁₈N₄O: 331.2 (MH⁺).

3-amino-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-6-phenylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.04 (d, 1H, 8.87 (s, 1H), 8.18 (m, 2H), 7.72(br s, 2H), 7.49-7.18 (m, 7H), 5.60 (m, 1H), 3.02 (m, 1H), 2.86 (m, 1H),2.44 (m, 1H), 2.21 (m, 1H); MS (EI) for C₂₀H₁₈N₄O: 331.2 (MH⁺).

3-amino-N-(2,3-dihydro-1H-inden-2-yl)-6-phenylpyrazine-2-carboxamide: ¹HNMR (400 MHz, d₆-DMSO): 9.04 (d, 1H), 8.87 (s, 1H), 8.18 (m, 2H), 7.72(br s, 2H), 7.49-7.18 (m, 7H), 5.60 (m, 1H), 3.02 (m, 1H), 2.86 (m, 1H),2.44 (m, 1H), 2.21 (m, 1H); MS (EI) for C₂₀H₁₈N₄O: 331.2 (MH⁺).

3-amino-N-cyclopentyl-6-phenylpyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): 8.89 (d, 1H), 8.82 (s, 1H), 8.12 (m, 2H), 7.61 (br s, 2H),7.46-7.15 (m, 7H), 4.79 (m, 1H), 3.28 (m, 2H), 3.11 (m, 2H); MS (EI) forC₁₆H₁₈N₄O: 283.2 (MH⁺).

3-amino-N-cyclopropyl-6-phenylpyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): 8.83 (s, 1H), 8.65 (s, 1H), 8.13 (m, 2H), 7.65 (br s, 2H),7.49-7.30 (m, 3H), 2.85 (m, 1H), 0.72 (m, 4H); MS (EI) for C₁₄H₁₄N₄O:255.4 (MH⁺).

Example 2

3-Amino-6-naphthalen-1-ylpyrazine-2-carboxamide

Methyl 3-amino-6-naphthalen-1-ylpyrazine-2-carboxylate: To a solution ofmethyl 3-amino-6-bromopyrazine-2-carboxylate (0.18 g, 0.74 mmol) inN,N-dimethylformamide (10 mL) were added[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex withdichloromethane (1:1, 60 mg, 0.07 mmol), 1-naphthylboronic acid (0.32 g,1.89 mmol), and triethylamine (0.15g, 1.52 mmol). The solution wasdegassed with nitrogen for 3-5 min. The reaction was then heated to85-90° C. overnight. The reaction was cooled to room temperature anddiluted with ethyl acetate (300 mL). The crude solution was passedthrough a pad of silica gel under vacuum. The filtrate was washed withsaturated aqueous sodium bicarbonate (50 mL) and saturated aqueoussodium chloride (50 mL). The organic layer was dried over magnesiumsulfate, filtered and concentrated at reduced pressure to afford impureproduct. Column purification on silica (8:2 hexanes/ethyl acetate)afforded methyl 3-amino-6-naphthalen-1-ylpyrazine-2-carboxylate (80 mg,39% yield) as yellow solid: ¹H NMR (400 MHz, CDCl₃): δ 8.52 (br s, 1H),8.12 (br s, 1H), 7.92 (m, 2H), 7.52 (m, 5H), 4.02 (s, 3H); MS (EI) forC₁₆H₁₃N₃O₂: 280 (MHz).

3-amino-6-naphthalen-1-ylpyrazine-2-carboxamide: A solution of methyl3-amino-6-naphthalen-1-ylpyrazine-2-carboxylate (80 mg, 0.29 mmol) inmethanol (30 mL) was saturated with ammonia gas at 0° C. in ahigh-pressure test tube. The reaction tube was tightly sealed and heatedto 80-90° C. for 4h. Reaction cooled to room temperature and evaporatedat reduced pressure to afford3-amino-6-naphthalen-1-ylpyrazine-2-carboxamide (59 mg, 79% yield) asyellow product: ¹H NMR (400 MHz, CDCl₃): δ 8.80 (s, 1H), 8.10 (d, 1H),7.90 (d, 2H), 7.58 (m, 6H); MS (EI) for C₁₅H₁₂N₄O: 265 (MH⁺).

3-amino-6-(3-chlorophenyl)pyrazine-2-carboxamide: To a 15 mL sealed tubewas added methyl 3-amino-6-(3-chlorophenyl)pyrazine-2-carboxylate (65mg, 0.246 mmol) and methanol (8 mL). The suspension was cooled to 0° C.and NH₃ (g) was bubbled until saturation was achieved. The tube wassealed and heated at 85° C. overnight with stirring. During initialheating, the reaction mixture became homogeneous. The tube was removedfrom the heat and allowed to cool to room temperature. Upon cooling ayellow, needle-like precipitate formed. The precipitate was collected onfilter paper to give 3-amino-6-(3-chlorophenyl)pyrazine-2-carboxamide(53.9 mg, 88% yield) as a yellow solid: ¹H NMR (400 MHz, d6-DMSO): δ8.88 (s, 1H), 8.42 (br s, 2H), 8.30 (t, 1H), 8.11 (d, 1H) 7.69 (br s,2H), 7.46-7.40 (m, 2H); MS (EI) for C₁₁H₉N₄OCl: 249 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-naphthalen-2-ylpyrazine-2-carboxamide: ¹H NMR (400 M&z,d₆-DMSO): δ 9.02 (s, 1H), 8.80 (s, 1H), 8.40 (m, 2H), 8.02 (m, 3H), 7.80(br s, 1H), 7.50 (t, 2H); MS (EI) for C₁₅H₁₂N₄O: 265 (MH⁺).

3-amino-6-biphenyl-4-ylpyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): δ 8.90 (s, 1H), 8.38 (br s, 1H), 8.30 (d, 2H), 7.70 (m, 5H),7.50 (m, 2H), 7.34 (m, 1H); MS (EI) for C₁₇H₁₄N₄O: 291 (MH⁺).

3-amino-6-(1-benzofuran-2-yl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): δ 8.85 (s, 1H), 8.60 (br s, 1H), 7.80 (s, 1H), 7.60 (m, 3H),7.30 (m, 2H); MS (EI) for C₁₃H₁₀N₄O: 255 (MH⁺).

3-amino-6-biphenyl-3-ylpyrazine-2-carboxamide: ¹H NMR (400 MHz, CDCl₃):v8.70 (s, 1H), 8.10 (s, 1H), 7.85 (d, 2H), 7.65 (t, 3H), 7.55 (t, 1H),7.45 (t, 3H), 7.40 (t, 1H); MS (EI) for C₁₇H₁₄N₄O: 291 (MH⁺).

3-[5-amino-6-(aminocarbonyl)pyrazin-2-yl]benzoic acid: ¹H NMR (400 MHz,d₆-DMSO): δ 8.95 (s, 1H), 8.80 (br s, 2H), 8.50 (s, 1H), 8.30 (d, 1H),7.98 (d, 1H), 7.60 (br t, 1H); MS (EI) for C₁₂H₁₀N₄O₃: 259 (MH⁺).

3-amino-6-{4-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide: ¹H NMR(400 MHz, d₆-DMSO): δ 8.80 (s, 1H), 8.30 (br s, 1H), 8.10 (d, 2H), 7.65(br s, 1H), 7.49 (d, 2H), 7.40 (t, 2H), 7.35 (t, 1H), 7.10 (d, 2H), 5.20(s, 2H); MS (EI) for C₁₈H₁₆N₄O₂: 321 (MH⁺).

3-amino-6-(2-chlorophenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.53 (s, 1H), 7.76-7.73 (m, 1H), 7.59-7.56 (m, 1H),7.46-7.43 (m, 2H); MS (EI) for C₁₁H₉N₄OCl: 249 (MH⁺).

3-amino-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.82 (s, 1H), 7.69-7.65 (m, 4H), 7.33 (t, 1H), 6.91 (dd,1H), 3.82 (s, 3H); MS (EI) for C₁₂H₁₂N₄O₂: 245 (MH⁺).

3-amino-6-(2-methylphenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.38 (s, 1H), 7.48-7.47 (m, 1H), 7.30-7.28 (m, 3H); MS (EI)for C₁₂H₁₂N₄O: 229 (MH⁺)

3-amino-6-[2-(methyloxy)phenyl]pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.72 (s, 1H), 7.94-7.91 (m, 1H), 7.36-7.34 (m, 1H),7.14-7.12 (m, 1H), 7.07-7.05 (m, 1H), 3.86 (s, 3H); MS (EI) forC₁₂H₁₂N₄O₂: 245 (MH⁺).

3-amino-6-(2,4-difluorophenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.59 (s, 1H), 8.28-8.26 (m, 2H), 7.17 (br s, 2H), 7.38-7.37(m, 1H), 7.20 (m, 1H); MS (EI) for C₁₁H₈N₄OF₂: 251 (MH⁺).

3-amino-6-(3-fluorophenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.89 (s, 1H), 8.11 (d, 1H), 7.98 (d, 1H), 7.48-7.46 (m, 1H),7.17-7.16 (m, 1H); MS (EI) for C₁₁H₉N₄OF: 233 (MH⁺).

3-amino-6-(3,4-difluorophenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.88 (s, 1H), 8.41-8.35 (m, 1H), 8.02 (m, 1H), 7.52-7.45 (m,1H); MS (EI) for C₁₁H₈N₄OF₂: 251 (MH⁺).

3-amino-6-(4-fluorophenyl)-N-methylpyrazine-2-carboxamide: ¹H NMR (400MHz, d6-DMSO): δ 8.84 (m, 2H), 8.25-8.22 (m, 2H), 7.31-7.26 (m, 2H),2.84 (d, 3H); MS (EI) for C₁₂H₁₁N₄OF: 247 (MH⁺).

3-amino-6-{3-[(trifluoromethyl)oxy]phenyl}pyrazine-2-carboxamide: ¹H NMR(400 MHz, d6-DMSO): δ 8.91 (s, 1H), 8.23 (s, 1H), 8.20-8.18 (m, 1H),7.59-7.54 (t, 1H), 7.35-7.33 (d, 1H); MS (EI) for C₁₂H₉N₄O₂F₃: 299(MH⁺).

3-amino-6-(3-methylphenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d6-DMSO): δ 8.82 (s, 1H), 8.00 (s, 1H), 7.93-7.91 (d, 1H), 7.34-7.31 (t,1H), 7.18-7.16 (m, 1H), 2.38 (s, 3H), MS (EI) for C₁₂H₁₂N₄O: 229 (MH⁺)

3-amino-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide: ¹H NMR(400 MHz, d6-DMSO): δ 8.84 (s, 1H), 7.78-7.77 (m, 1H), 7.71-7.70 (m,2H), 7.50-7.59 (m, 2H), 7.43-7.39 (m, 2H), 7.38-7.31 (m, 2H), 7.02-6.99(m, 1H), 5.21 (s, 2H); MS (EI) for C₁₈H₁₆N₄O₂: 321 (MH⁺).

3-amino-6-(3-hydroxyphenyl)pyrazine-2-carboxamide: To a 25 mL recoveryflask was added3-amino-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide (33 mg,0.103 mmol) and ethyl acetate (10 mL). A catalytic amount of 10% Pd/Cwas added. The flask was sealed with a septum and fitted with an H₂balloon. The reaction mixture was stirred overnight at room temperature.The reaction mixture was passed through a Celite pad. The filtrate wasconcentrated to give 3-amino-6-(3-hydroxyphenyl)pyrazine-2-carboxamide(23 mg, 96% yield) as a yeloow powder. ¹H NMR (400 MHz, d6-DMSO): δ 9.47(s, 1H), 8.74 (s, 1H), 7.55-7.53 (m, 1H), 7.46 (m, 1H), 7.25-7.22 (t,1H), 6.78-6.76 (m, 1H); MS (EI) for C₁₁H₁₀N₄O₂: 231 (MH⁺).

3-amino-N,N-dimethyl-6-phenylpyrazine-2-carboxamide: ¹H NMR (400 MHz,CDCl₃): 8.54 (s, 1H), 7.89 (m, 2H), 7.48-7.33 (m, 3H), 5.88 (br s, 2H),3.33 (s, 3H), 3.17 (s, 3H); MS (EI) for C₁₃H₁₄N₄O: 243.1 (MH⁺).

3-amino-6-[4-(ethyloxy)phenyl]pyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): 8.78 (s, 1H), 8.28 (s, 1H), 8.08 (m, 2H), 7.66 (s, 1H), 7.56(br s, 2H), 6.98 (m, 2H), 4.08 (q, 2H), 1.35 (t, 3H); MS (EI) forC₃₁H₁₄N₄O₂: 259.4 (MH⁺).

3-amino-6-[3-(ethyloxy)phenyl]pyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): 8.85 (s, 1H), 8.30 (s, 1H), 7.96-7.28 (m, 6H), 6.92 (m, 1H),4.13 (q, 2H), 1.35 (t, 3H); MS (EI) for C₁₃H₁₄N₄O₂: 259.4 (NH⁺).

3-amino-6-(1,3-benzodioxol-5-yl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): 8.78 (s, 1H), 8.36 (s, 1H), 7.85 (s, 1H), 7.79-7.37 (m, 4H),6.96 (d, 1H), 6.07 (s, 2H); MS (EI) for C₁₂H₁₀N₄O₃: 259.4 (MH⁺).

3-amino-6-[3-(aminocarbonyl)phenyl]pyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.92 (s, 1H), 8.54 (s, 1H), 8.40 (s, 1H), 8.32 (d, 1H),8.16 (s, 1H), 7.95 -7.42 (m, 6H); MS (EI) for C₁₂H₁₁N₅O₂: 258.4 (MH⁺).

6-[3-(acetylamino)phenyl]-3-aminopyrazine-2-carboxamide: ¹H NMR (400MHz, d6-DMSO): 9.99 (s, 1H), 8.72 (s, 1H), 8.11 (m, 2H), 7.94-7.46 (m,5H), 7.37 (m, 1H), 2.06 (s, 3H); MS (EI) for C₁₃H₁₃N₅O₂: 272.4 (MH⁺).

3-amino-6-[4-(dimethylamino)phenyl]pyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.73 (s, 1H), 8.21 (s, 1H), 7.97 (m, 2H), 7.64 (s, 1H),7.45 (br s, 2H), 6.76 (m, 2H), 2.95 (s, 6H); MS (EI) for C₁₃H₁₅N₅O:258.4 (MH⁺).

methyl 3-[5-amino-6-(aminocarbonyl)pyrazin-2-yl]benzoate: ¹H NMR (400MHz, d₆-DMSO): 8.90 (s, 1H), 8.57 (s, 1H), 8.48 (m, 1H), 8.31 (s, 1H),8.00-7.42 (m, 5H), 3.90 (s, 3H); MS (EI) for C₁₃H₁₂N₄O₃: 273.4 (MH⁺).

3-amino-N-methyl-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.82 (m, 2H), 7.92-7.19 (m, 10H), 7.03 (m,1H), 5.22 (s, 2H), 2.85 (s, 3H); MS (EI) for C₁₉H₁₈N₄O₂: 335.4 (MH⁺).

3-amino-6-(3-hydroxyphenyl)-N-methylpyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 9.49 (s, 1H), 8.73 (m, 2H), 7.87-7.34 (m, 4H), 7.25 (m,1H), 6.79 (m, 1H), 2.85 (d, 3H); MS (EI) for C₁₂H,₂N₄O₂: 245.4 (MHz.MHz, d₆-DMSO): 8.85 (m, 2H), 8.15 (m, 2H), 7.68 (br s, 2H), 7.47 (m,2H), 7.40 (m, 1H), 3.50 (m, 4H), 3.29 (s, 311); MS (EI) for C₁₄H₁₆N₄O₂:273.4 (MH⁺).

N-[2-(acetylamino)ethyl]-3-amino-6-phenylpyrazine-2-carboxamide: ¹H NMR(400 MHz, 4-DMSO): 8.94 (t, 1H), 8.86 (s, 1H), 8.19 (m, 2H), 8.05 (t,1H), 7.66 (br s, 1H), 7.46 (m, 2H), 7.38 (m, 1H), 3.38 (m, 2H), 3.27 (m,2H), 1.83 (s, 3H); MS (EI) for C₁₅H₁₇N₅O₂: 300.4 (MH⁺).

3-amino-6-phenylpyrazine-2-carbohydrazide: ¹H NMR (400 MHz, d₆-DMSO):10.02 (s, 1H), 8.82 (s, 1H), 8.19 (m, 2H), 7.58 (br s, 2H), 7.43 (m,2H), 7.35 (m, 2H), 7.32 (m, 1H), 4.57 (m, 2H); MS (EI) for C₁₁H₁₁N₅O:230.3 (MH⁺).

3-amino-N-hydroxy-6-phenylpyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): 11.42 (s, 1H), 9.12 (s, 1H), 8.83 (s, 1H), 8.20 (m, 2H; 7.53br s, 2H, 7.42 (m, 2H), 7.36 (m, 1H); MS (EI) for C₁₁H₁₀N₄O₂: 231.3(MH⁺).

3-amino-N-(2-hydroxyethyl)-6-(3-methylphenyl)pyrazine-2-carboxamide: Asolution of 3-amino-6-bromo-2-carbomethoxypyrazine (100 mg, 0.4 mmol )and 2-aminoethanol (500 mg, 8.2 mmol ) in THF (5 mL) was heated atreflux for 2 days. The reaction mixture was cooled, diluted with ethylacetate (20 mL), washed with water then brine, dried over sodiumsulfate, filtered, and concentrated. The oily residue was purified byflash chromatography (silica gel, eluted with ethyl acetate-hexanesgradient from 15% to 80% yield) to give3-amino-N-(2-hydroxyethyl)-6-bromo-pyrazine-2-carboxamide, a pale yellowoil, (108 mg, 96% yield) MS (EI) for C₇H₉BrN₄O₂: 262 (MH⁺).

The intermediate3-amino-N-(2-hydroxyethyl)-6-bromopyrazine-2-carboxamide (108 mg, 0.4mmole),[1,1′bis-(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethanecomplex (19 mg, 0.04 mmol), 3-methylphenylboronic acid (67 mg, 0.5 mmol)in DMF (2 mL) was de-gassed with nitrogen. Triethylamine (0.12 mL, 0.8mmol) was then added and the resulting mixture was heated at 85° C. for2.5 hours. The reaction mixture was cooled to room temperature, dilutedwith ethyl acetate (10 mL), filtered over silica gel, washed withsaturated sodium bicarbonate solution (10 mL), dried over sodiumsulfate, filtered, and concentrated. The oily residue was purified byflash chromatography (silica gel, eluted with ethyl acetate-hexanesgradient from 15% to 80% yield) to give methyl3-amino-N-(2-hydroxyethyl)-6-(3-methylphenyl)pyrazine-2-carboxamide as asolid: (95 mg, 84% yield): ¹H NMR (400 MHz, DMSO-d₆): 8.78 (s, 1H),8.78-8.61 (b, 1H), 7.89 (s, 1H), 7.49-7.52 (t, 1H), 7.51-7.49 (d, 1H),7.14-7.12 (d,1H), 3.50-3.35 (m, 2H), 2.89-70 (m, 2H), 2.51 (s, 3H): MS(EI) for C₁₄H₁₆N₄O₂: 273 (MH⁺).

Example 3

3-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2-carboxamide

3-amino-6-bromo-N-methyl-2-pyrazinecarboxamide: An ice-cooled solutionof 50 g of methyl 3-amino-6-bromo-pyrazine-2-carboxylate in 500 mL ofMeOH was saturated with methylamine gas. The reaction was then heated at85° C. in a sealed, stainless steel Parr pressure vessel for 2 h, andcooled to room temperature, and then on an ice water bath. The mixturewas concentrated to an oil on a rotary evaporator under reducedpressure. The crude oil was dissolved in EtOAc and washed with water,dried (Na₂SO₄), filtered, and concentrated to give 43.9 g (88.0% yield)of product as a solid.

3-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2-carboxamide:A suspension of 3-amino-6-bromo-N-methyl-2-pyrazinecarboxamide (69.3 mg,0.3 mmol), [4-(tetrahydro-2H-pyran-2-yloxy)phenyl boronic acid (111 mg,0.5 mmol) [1,1-bis(diphenylphosphino)-ferrocene]dichloropalladium(II)complex with dichloromethane (1:1) (20.4 mg, 0.025 mmol), andtriethylamine (121 mg,1.2 mmol) in DMF (20 mL) was stirred at 80° C.under nitrogen for 12 h. DMF was removed under vacuo. The residue wasextracted with ethyl acetate (3×50 mL). The organic layers were washedwith brine (10 mL) then dried over anhydrous sodium sulfate. Filtration,concentration and column chromatography on silica gave3-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2-carboxamide(68.3 mg, 70% yield) as a yellow solid. ¹H NMR (400 MHz, d₆-DMSO): 8.8(m, 2H), 8.1 (d, 2H), 7.1 (d, 2H), 5.56 (s, 1H), 3.78 (m, 2H), 3.45 (m,2H), 1.98-1.43 (m, 6H); MS (EI) for C₁₇H₂₀N₄O₃: 329 (MH+).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-[4-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide: ¹H NMR(400 MHz, CDCl₃): δ 8.52 (s, 1H), 8.02 (br s, 1H), 7.80 (d, 2H), 7.00(br d, 2H), 7.55 (t, 2H), 412 (q, 2H), 3.02 (d, 3H), 1.43 (t, 3H); MS(EI) for C₁₄H₁₆N₄O₂: 273 (MH⁺).

3-amino-N-methyl-6-(3-methylphenyl)pyrazine-2carboxamide: ¹H NMR (400MHz, CDCl₃): δ 8.60 (s, 1H), 8.01 (br s, 1H), 7.64 (br d, 2H), 7.38 (t,1H), 7.25 (br d, 1H), 3.02 (d, 3H), 2.42 (s, 3H); MS (EI) for C₁₃H₁₄N₄O:243 (MH⁺).

3-amino-N-methyl-6-[4-(methyloxy)phenyl]pyrazine-2-carboxamide: ¹H NMR(400 M, CDCl₃): δ 8.57 (s, 1H), 8.02 (br s, 1H), 7.80 (br d, 2H), 7.02(br d, 2H), 3.84 (s, 3H), 3.10 (d, 3H); MS (EI) for C₁₃H₁₄N₄O₂: 259(MH⁺)

3-amino-N-methyl-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide: ¹H NMR(400 MHz, CDCl₃): δ 8.60 (s, 1H), 8.02 (br s, 1H), 7.40 (m, 3H), 6.90(br d, 1H), 3.92 (s, 3H, 3.02 (br s, 3H; MS (EI) for C₁₃H₁₄N₄O₂: 259(MH⁺).

3-amino-6-(4-fluoro-3-methylphenyl)-N-methylpyrazine-2-carboxamide: ¹HNMR (400 MHz, CDCl₃): δ 8.52 (s, 1H), 7.94 (br s, 1H), 7.65 (m, 2H),7.12 (t, 1H), 3.02 (d, 3H), 2.40 (s, 3H); MS (EI) for C₁₃H₁₃N₄O F: 261(MH⁺).

3-amino-N-methyl-6-pyridin-3-ylpyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): δ 9.40 (br s, 1H), 8.94 (br s, 2H), 8.54 (m, 2H), 7.44 (t,1H), 2.90 (br s, 3H), MS (EI) for C₁₁H₁₁N₅O: 230 (MH⁺).

3-amino-6-[4-(dimethylamino)phenyl]-N-methylpyrazine-2-carboxamide: ¹HNMR (400 M, CDCl₃): δ 8.58 (s, 1H), 8.12 (br s, 1H), 7.75 (br d, 2H),6.80 (br d, 2H), 3.02 (m, 9H); MS (EI) for C₁₄H₁₇N₅O: 272 (MH⁺).

3-amino-N-methyl-6-{4-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.80 (br s, 1H), 8.80 (br s, 2H), 8.15 (br d,2H, 7.30 (br d, 2H), 3.02 (br s, 3H), 2.80 (br s, 3H); MS (EI) forC₁₃H₁₅N₅O₃S: 322 (MH⁺).

3-amino-6-(3,5-dimethylphenyl)-N-methylpyrazine-2-carboxamide: ¹H NMR(400 MHz, CDCl₃): 8.60 (s, 1H), 8.02 (br s, 1H), 7.45 (br d, 2H), 7.05(br s, 1H), 3.02 (br s, 3H), 2.40 (br s, 6H); MS (EI) for C₁₄H₁₆N₄O: 257(MH⁺).

6-(4-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamide: ¹H NMR (400MHz, CDCl₃): 8.70 (br s, 1H), 8.05 (br d, 2H), 7.95 (br d, 3H, 3.10 (d,3H), 2.60 (s, 3H); MS (EI) for C₁₄H₁₄N₄O₂: 271 (MH⁺).

3-amino-6-[3,4-bis(methyloxy)phenyl]-methylpyrazine-2-carboxamide: ¹HNMR (400 MHz, CDCl₃): 8.58 (s, 1H), 7.95 (br s, 1H), 7.40 (dd, 1H), 7.36(d, 1H), 6.82 (d, 1H), 4.02(s, 3H), 3.92(s, 3H), 3.02 (d, 3H); MS (EI)for C₁₄H₁₆N₄O₃: 289 (MH⁺).

3-amino-6-(3-cyanophenyl)-N-methylpyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.89 (m, 2H), 8.70 (br s, 1H), 8.45 (d, 1H), 7.80 (d,1H), 7.60 (t, 1H), 2.82 (br s, 3H); MS (EI) for C₁₃H₁₁N₅O: 254 (MH⁺).

3-amino-N-methyl-6-[3-(1H-tetrazol-5-yl)phenyl]pyrazine-2-carboxamide:To a solution of3-amino-6-(3-cyanophenyl)-N-methylpyrazine-2-carboxamide (93 mg, 0.37mmol) in dry N,N-dimethylformamide (1 mL) were added sodium azide (27mg, 0.41 mmol), and ammonium chloride (22 mg, 0.41 mmol). The reactionwas heated to 100-110° C. overnight. Reaction cooled to room temperatureand treated with saturated aqueous sodium bicarbonate (20 mL). Theaqueous layer was washed with ethyl acetate (2×30 mL). The sodiumbicarbonate layer was cooled to 0° C. and neutralized with 2.0 Nhydrochloric acid until the pH of the solution became in the 2-3 range.The aqueous layer was extracted with ethyl acetate (100 mL) and washedwith water (20 mL) and saturated aqueous sodium chloride (30 mL), driedover magnesium sulfate, filtered, and concentrated at reduced pressureto afford3-amino-N-methyl-6-[3-(1H-tetrazol-5-yl)phenyl]pyrazine-2-carboxamide(25 mg, 23% yield) as light yellow solid. ¹H NMR (400 MHz, d₆-DMSO):8.92 (s, 1H), 8.84 (m, 1H), 8.70 (br s, 1H), 8.40 (br d, 1H), 8.12 (brd, 1H), 7.70 (t, 1H), 2.92 (br s, 3H); MS (EI) for C₁₃H₁₂N₈O: 297 (MH⁺).

3-amino-6-[3-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide: ¹H NMR(400 MHz, d₆-DMSO): 8.83 (s, 1H), 8.81 (m, 1H), 7.70 (m, 2H), 7.62 (brs, 2H), 7.36 (m, 1H), 6.93 (m, 1H), 4.12 (q, 2H), 2.85 (d, 3H), 1.36 (t,3H); MS (EI) for C₁₄H₁₆N₄O₂: 273.4 (MH⁺).

3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.66 (m, 2H), 7.58 (br s, 2H), 7.27 (m, 2H), 7.11 (m,1H), 6.59 (m, 1H), 5.09 (s, 2H), 2.85 (d, 3H); MS (EI) for C₁₂H₁₃N₅O:244.4 (MH⁺).

6-[3-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide: ¹H NMR(400 MHz, d₆-DMSO): 10.01 (s, 1H), 8.69 (m, 2H), 8.03 (m, 1H), 7.83 (m,1H), 7.78 (m, 1H), 7.63 (br s, 2H), 7.38 (m, 1H), 2.85 (d, 3H), 2.08 (s,3H); MS (EI) for C₁₂H₁₃N₅O: 286.4 (MH⁺).

3-amino-6-[3-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide: ¹HNMR (400 MHz, d₆-DMSO): 8.82 (s, 1H), 8.78 (m, 1H), 8.04 (m, 2H), 7.64(br s, 2H), 7.42 (m, 1H), 7.35 (m, 1H), 5.23 (t, 1H), 4.58 (d, 2H), 2.86(d, 3H); MS (EI) for C₁₃H₄N₄O₂: 259.4 (MH⁺).

3-amino-6-[4-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide: ¹HNMR (400 MHz, d₆-DMSO): 8.84 (s, 1H), 8.82 (m, 1H), 8.14 (d, 2H), 7.62(br s, 2H), 7.40 (d, 2H), 5.24 (t, 1H), 4.55 (d, 2H), 2.85 (d, 3H); MS(EI) for C₁₃H₁₄N₄O₂: 259.4 (MH⁺).

3-amino-N-methyl-6-{3-[(1E)-N-methylethanimidoyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.86 (s, 1H), 8.81 (m, 1H), 8.35 (m, 1H),8.22 (m, 1H), 7.80 (m, 1H), 7.68 (br s, 2H), 7.48 (t, 1H), 3.29 (s, 3H),2.85 (d, 3H), 2.30 (s, 3H); MS (EI) for C₁₅H₁₇N₅O: 284.4 (MH⁺).

6-[4-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide: ¹H NMR(400 MHz, d₆DMSO): 10.06 (s, 1H), 8.80 (s, 1H), 8.11 (d, 2H), 7.67 (d,2H), 7.60 (br s, 2H), 2.84 (d, 3H), 2.07 (s, 3H); MS (EI) forC₁₄H₁₅N₅O₂: 286.4 (MH⁺).

3-amino-N-methyl-6-{3-[(methylamino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.90 (s, (1H), 8.84 (m, 1H), 8.54 (m, 1H),8.47 ((s, 1H), 8.34 (d, 1H), 7.82 (d, 1H), 7.72 (br s, 2H), 7.56 (t,1H), 2.84 (d, 3H), 2.82 (d, 3H); MS (EI) for C₁₄H₁₅N₅O₂: 286.4 (MH⁺).

6-(3-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.94 (s, 1H), 8.87 (m, 1H), 8.57 (t, 1H), 8.48 (m, 1H),7.93 (m, 1H), 7.75 (br s, 2H), 7.62 (t, 1H), 2.86 (d, 3H), 2.70 (s, 3H);MS (EI) for C₁₄H₁₄N₄O₂: 271.4 (MH⁺).

3-amino-N-methyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide,¹H NMR (400 MHz, d₆ DMSO), 9.14 (t, 1H), 8.91 (s, 1H), 8.84 (m, 1H),8.54 (t, 1H), 8.39 (m, 1H), 7.89 (m, 1H), 7.70 (br s, 2H), 7.58 (t, 1H),7.38-7.32 (m, 4H), 7.24 (m, 1H), 4.54 (d, 2H), 2.86 (d, 3H); MS (EI) forC₂₀H₁₉N₅O₂:362.1 (MH⁺).

3-amino-6-[3-(aminocarbonyl)phenyl]-N-methylpyrazine-2carboxamide: ¹HNMR (400 MHz, d₆-DMSO/CD₃OD): 8.90 (m, 1H), 8.57 (m, 1H), 8.32 (m, 1H),7.91 (m, 1H), 7.57 (m, 1H), 2.90 (m, 3H); MS (EI) for C₁₃H₁₃N₅O₂: 272.0(MH⁺).

3-amino-6-{3-[(dimethylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.86 (m, 2H), 8.20 (m, 2H), 7.70 (br s, 2H),7.49 (m, 1H), 7.34 (m, 1H), 3.02 (s, 3H), 2.92 (s, 3H), 2.83 (m, 3H); MS(EI) for C₁₅H₁₇N₅O₂: 300.4 (MH⁺).

3-amino-N-methyl-6-[4-(methylsulfonyl)phenyl]pyrazine-2-carboxamide: ¹HNMR (400 MHz, d₆-DMSO), 8.95 (m, 2H), 8.11 (br s, 2H), 7.96 (m, 2H),3.26 (s, 3H), 2.85 (m, 3H); MS (EI) for C₁₃H₁₄N₄O₃S: 307.4 (MH⁺).

3-amino-6-(3-aminophenyl)-N-ethylpyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.71 (m, 1H), 8.65 (s, 1H), 7.60 (br s, 2H), 7.27 (m,2H), 7.11 (m, 1H), 6.59 (m, 1H), 5.10 (s, 2H), 3.34 (m, 2H), 1.16 (m,3H); MS (EI) for C₁₃H₁₅N₅O: 258.3 (MH⁺).

3-amino-N-methyl-6-pyrimidin-5-ylpyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 9.57 (m, 2H), 9.15 (s, 1H), 8.98 (m, 2H), 8.94 (s, 1H),2.8 (d, 3H), MS (EI) for C₁₀ H₁₀N₆O₂: 231 (MH⁺).

3-amino-N-methyl-6-[3-(methylsulfonyl)phenyl]pyrazine-2-carboxamide: ¹HNMR (400 MHz, d₆-DMSO): 8.98 (s, 1H), 8.84 (m, NH), 8.52 (m, 2H), 7.85(d, 1H), 7.74 (t, 1H), 3.15 (s, 3H); 2.85 (d, 3H); MS (EI) forC₁₃H₁₄N₄O₃S: 307 (MH⁺).

3-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2-carboxamide:Prepared as above.

3-amino-N-methyl-6-(4-hydroxyoxyphenyl)pyrazine-2-carboxamide:3-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2-carboxamide(63 mg) was suspended in methanol followed by addition of aqueoushydrochloric acid (2 mL). The mixture was stirred for 15 min., pouredinto water (10 mL), and extracted with ethyl acetate (10 mL). Theorganic layer was washed with saturate aqueous sodium chloride thendried over anhydrous sodium sulfate. Filtration, concentration andcolumn chromatography on silica followed by drying in vacuo afforded3-amino-N-methyl-6-(4-hydroxyoxyphenyl)pyrazine-2-carboxamide (30 mg,64% yield): ¹H NMR (400 MHz; DMSO-D₆): 9.62 (s, 1H); 8.78 (m, 1H); 8.82(m, 1H); 8.7 (s, 1H); 7.98 (d, 2H); 7.5 (br s, 1H); 6.8 (d, 2H); 2.85(d, 3H); MS (EI) for C₁₂H₁₂N₄O₂:245 (MH⁺).

3-amino-N-methyl-6-(3-thienyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz;DMSO-D₆): 8.85 (m, 1H); 8.76 (s, 1H); 8.25 (m, 1H); 7.92 (d, 1H); 7.64(m, 1H); 2.82 (d, 3H); MS (EI) for C₁₀H₁₀N₄OS: 235 (MH⁺).

3-amino-6-(1H-indol-5-yl)-N-methylpyrazine-2-carboxamide: ¹H NMR (400MHz; DMSO-D₆): 11.2 (s, 1H); 8.8 (s, 1H); 8.75 (m, 1H); 8.3 (s, 1H); 7.9(d, 1H); 7.4 (d, 1H); 7.35 (t, 1H); 6.45 (s, 1H); 2.85 (d, 3H); MS (EI)for C₁₄H₁₃N₅O: 268 (MH⁺).

3-amino-N-methyl-6-(2-thienyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz;DMSO-D₆): 8.7 (s, 1H); 8.48 (m, 1H); 7.75 (d, 1H); 7.62 (br s, 2H); 7.57(d, 1H); 7.15 (t, 1H); 2.85 (d, 3H); MS (EI) for C₁₀H₁₀N₄OS: 235 (MH⁺):

3-amino-N-methyl-6-pyridin-4-ylpyrazine-2-carboxamide: ¹H NMR (400 MHz;CD₃OD): 8.82 (s, 1H); 8.55 (d, 2H); 8.1 (d, 2H); 2.85 (d, 3H); MS (EI)for C₁₁H₁₁N₅O: 230 (MH⁺).

3-amino-N-methyl-6-naphthalen-2-ylpyrazine-2-carboxamide: ¹H NMR (400MHz, d₆-DMSO): 8.99 (s, 1H), 8.89 (m, 1H), 8.69 (s, 1H), 8.38 (d, 1H),7.98 (d, 2H), 7.92 (d, 1H), 7.74 (br s, 2H), 7.52 (m, 2H), 2.88 (d, 3H);MS (EI) for C₁₆H₁₄N₄O: 279.2 (MH^(+).)

3-amino-N-methyl-6-quinolin-3-ylpyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): 9.76 (d, 1H), 9.05 (s, 2H), 8.99 (m, 1H), 8.02 (m, 2H), 7.89(br s, 2H), 7.75 (m, 1H), 7.63 (m, 1H), 2.88 (d, 3H); MS (EI) forC₁₅H₁₃N₅O: 280.2 (MH⁺).

Example 4

3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid

N-methyl benzamides, where A is —C(═O)— and E is —N(H)CH₃ according toformula I, were prepared in analgous fashion as described above startingfrom 3-Amino-6-bromo-pyrazine-2-carboxylic acid methylamide.

Methyl 3-[5-amino-6-(methylamino)carbonyl)pyrazin-2-yl}benzoate: To astirred mixture of 3-amino-6-bromo-pyrazine-2-carboxylic acidmethylamide (2.29 g, 9.91 mmol, 1.00 equiv.),3-methoxycarbonylphenylboronic acid (Digital Specialty Chemicals, Inc.,2.68 g, 14.9 mmol, 1.50 equiv.), triethylamine (2.90 g, 28.6 mmol, 2.88equiv.) in 30 mL of DMF was added[1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complexwith dichloromethane (1:1), (Aldrich Chemical Company, 405 mg, 0.496mmol, 0.050 equiv.) The stirred mixture was warmed to 80-90° C. for 24hr and then concentrated on a rotary evaporator under reduced pressure.The residue was dissolved in 250 mL of EtOAc, washed three times with 10mL of 1 N aqueous NaOH, and then saturated aqueous NaCl. The organicsolution was filtered through celite, and then concentrated on a rotaryevaporator under reduced pressure. The crude product was purified bysilica gel chromatography, using EtOAc as eluent, to afford the titlecompound (2.10 g, 74% yield).

3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid: A flaskwas charged with methyl3-[5-amino-6-(methylamino)carbonyl)pyrazin-2-yl}benzoate (2.86 g, 10mmol) and 30 mL of a solution of 2 N aqueous NaOH. The mixture wasrefluxed for 15 min. and then allowed to cool to room temperature. Themixture was extracted with ethyl acetate (10 mL). The pH of the aqueousphase was adjusted to pH between 2-3 with 10% aqueous HCl with stirring.The resulting pale yellow solid product was collected by filtration,washed with water, arid dried, to afford3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid (2.30 g84.5% yield): ¹H NMR (400 MHz; DMSO-d₆): 8.83 (s, 1H); 8.80 (s, 1H);8.51 (s, 1H); 8.41 (d, 1H); 7.93 (d, 1H); 7.93 (d, 1H); 7.65 (br s, 2H);7.58 (m, 1H); 2.84 (s, 3H); MS (EI) for C₁₃H₁₂N₄O₃: 273 (MH⁺).

3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:A flask was charged with3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid (48.9 mg,0.18 mmol), 1-hydroxybenzotriazole (HOBT, 39.7 mg, 0.294 mmol), 2.00 mLof tetrahydrofuran, 4-chlorobenzylamine (28.2 mg, 0.2 mmol) and1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (66.2 mg,0.353 mmol). The reaction was stirred at room temperature for 2 h. Thereaction was diluted with ethyl acetate, washed sequentially saturatedaqueous NaCl, saturated aqueous sodium carbonate, 1.0 M aqueoushydrochloric acid, and saturated aqueous sodium bicarbonate The organiclayer was dried over sodium sulfate, filtered, and concentrated on arotary evaporator under reduced pressure. The crude product was purifiedby chromatography on silica gel using EtOAc as the eluent. Afterconcentration, the product was triturated in 5% ethyl acetate inhexanes. The solid product was filtered, and after drying afforded3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide(39.8 mg, 50% yield). ¹H NMR (400 MHz; DMSO-d₆): 9.15 (m, 1H); 8.87 (s,1H); 8.80 (m, 1H); 8.50 (s, 1H); 8.35 (d, 1H); 7.85 (d, 1H); 7.53 (d,1H); 7.37 (m, 2H); 4.51 (d, 2H); 2.83 (s, 3H): MS (EI) for C₂₀H₁₈N₅O₂Cl:396 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-[(2-oxo-2-phenyl-ethylcarbamoyl)-phenyl]-pyrazine-2-carboxylicacid methylamide: ¹H NMR (400 MHz; DMSO-d₆): 9.13 (br s, 1H); 8.98 (brs, 1H); 8.90 (s, 1H); 8.65 (s, 1H); 8.38 (d, 1H); 8.07 (m, 2H); 7.84 (d,1H); 7.64 (m, 1H); 6.60 (m, 3H);4.81 (d, 2H); 2.83 (s, 3H): MS (EI) forC₂₁H₁₉N₅O₃: 390 (MH⁺).

3-amino-N-methyl-6-{3-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₁₈H₂₂N₆O₂: 355 (MH⁺).

3-amino-N-methyl-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₂₁H₂₁N₅O₂: 376 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₂₁H₂₁N₅O₃: 392 (MH⁺).

3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide;MS (EI) for C₂₂H₂₁N₅O₂: 388 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₂H₂₁N₅O₂: 388 (MH⁺).

3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H18N₅O₂Cl: 396 (MH⁺).

3-amino-N-methyl-6-(3-{[methyl(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₂₁H₂₁N₅O₂: 376 (MH⁺).

3-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H17N₅O₂Cl₂: 431 (MH⁺).

3-amino-N-methyl-6-[3-({[(4-methylphenyl)methyl]amino)carbonyl)phenyl]pyrazine-2-carboxamide;MS (EI) for C₂₁H₂₁N₅O₂: 376 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl]pyrazine-2-carboxamide:MS (EI) for C₂₁H₁₈N₅O₂F₃: 430 (MH⁺).

3-amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H₁₈N₅O₂F: 380 (MH⁺).

3-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.84 (s, 1H); 8.82 (m, 1H); 8.73(d, 1H); 8.47(m, 1H); 8.31 (d, 1H); 7.82 (d, 1H); 7.52 (t, 1H); 7.12-7.22 (m, 3H);4.76 (m, 1H); 3.20 (m, 2H); 3.0 (m, 2H) 2.82 (d, 3H); MS (EI) forC₂₂H₂₁N₅O₂: 388 (MH⁺).

3-amino-N-methyl-6-{3-[{[3-methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₂₁H₂₁N₅O₃: 392 (MH⁺).

3-amino-N-methyl-6-{3-[({(1R)-1-[4-(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.85 (s, 1H); 8.82 (m, 2H); 8.49(s, 1H); 8.38(d, 1H); 7.80 (d, 1H); 7.65 (br s, 2H); 7.57 (t, 1H); 7.30 (d, 2H); 6.87(d, 2H); 5.18 (m, 1H); 3.70 (m, 3H); 2.86 (s, 3H) 1.50 (d, 3H); MS (EI)for C₂₂H₂₃N₅O₃: 406 (MH⁺).

3-amino-N-methyl-6-{3-[({[2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₂₁H₁₈N₅O₂F₃: 430 (MH⁺).

3-amino-6-[3-({[(3-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H₁₈N₅O₂F: 380 (MH⁺)

3-amino-6-[3-({[1-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₁H₂₀N₅O₂F: 394 (MH⁺)

3-amino-6-{3-[({[2,3-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₄H₂₅N₃O₄: 420 (MH⁺)

3-amino-6-(3-{[bis(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₇H₂₅N₅O₂: 452 (MH⁺)

3-amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₂H₂₃N₅O₄: 422 (MH⁺)

3-amino-6-(3-{[ethyl(pyridin-4-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₁H₂₂N₆O₂: 391 (MH⁺)

3-amino-N-methyl-6-(3-{[4-(phenylmethyl)piperazine-1-yl]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₂₄H₂₆N₆O₂: 431 (MH⁺)

3-amino-N-methyl-6-[3-({[1-(phenylmethyl)piperidin-4-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.84 (s, 1H); 8.82 (m, 1H); 8.42(s, 1H); 8.36(br s, 1H); 7.80 (m, 1H); 7.65 (br s, 2H); 7.45 (t, 1H); 7.30 (m, 3H);3.23 (m, 1H); 3.47 (s, 2H); 2.85 (s, 3H) 1.84-2.04 (m, 8H); MS (EI) forC₂₅H₂₈N₆O₂: 445 (MH⁺)

3-amino-N-methyl-6-[3-({[(5-methylpyrazin-2-yl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:MS (EI) for C₁₉H₁₉N₇O₂: 378 (MH⁺)

3-amino-N-methyl-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₁₉H₁₈N₆O₂: 363 (MH⁺)

3-amino-N-methyl-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₁₉H₁₈N₆O₂: 363 (MH⁺)

3-amino-N-methyl-6-(3-{[(pyridin-4-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 9.21 (s, 1H); 8.89 (s, 1H); 8.26(s, 1H); 8.50(m, 3H); 8.39 (d, 1H); 7.86 (d, 1H); 7.57 (t, 1H); 7.33 (s, 1H); 4.55(s, 2H); 2.85 (s, 3H); MS (EI) for C₁₉H₁₈N₆O₂: 363 (MH⁺)

3-amino-6-[3-({[(3-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H₁₈N₅O₂Cl: 396 (MH⁺)

3-amino-6-(3-{[(cyclohexylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H₂₅N₅O₂: 368 (MH⁺)

3-amino-N-methyl-6-(3-{[(2-phenylpropyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₂₂H₂₃N₅O₂: 390 (MH⁺)

3-amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H₁₈N₅O₂Cl: 396 (H⁺)

3-amino-6-[3-({[2-(2-chlorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₁H₂₀N₅O₂Cl: 410 (MH⁺)

3-amino-N-methyl-6-{3-[({2-[2-(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₂₂H₂₃N₅O₃: 406 (MH⁺)

3-amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₁H₂₀N₅O₂F: 394 (MH⁺)

3-amino-N-methyl-6-[3-({[2-(2-thienyl)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:MS (EI) for C₁₉H₁₉N₅O₂S: 382 (MH⁺)

3-amino-6-{3-[(cyclohexylamino)carbonyl]phenyl}-3-N-methylpyrazine-2-carboxamide:MS (EI) for C₁₉H₂₃N₅O₂: 354 (MH⁺)

1,1-dimethylethyl4-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)piperidine-1-carboxylate:MS (EI) for C₂₄H₃₂N₆O₄: 469 (MH⁺)

3-amino-N-methyl-6-(3-{[(piperidin-4-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₁₉H₂₄N₆O₂: 369 (MH⁺)

3-amino-N-methyl-6-[3-({[(3S)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.62 (s, 1H); 8.35 (s, 1H); 8.03 (br s, 1H);7.98 (d, 1H); 7.52 (t, 1H); 7.3 (m, 5H); (m, 6.85 (d, 1H); 4.74 (m, 1H);3.65 (d, 2H); 2.8-3.1 (m, 4H); 2.8 (m, 1H); 2.65 (m, 1H); 2.4 (m, 1H);2.3 (m, 1H); 1.8 (m, 1H); MS (EI) for C₂₄H₂₆N₆O₂: 431 (MH⁺)

3-amino-N-methyl-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:MS (EI) for C₂₄H₂₆N₆O₂: 431 (MH⁺)

3-amino-N-methyl-6-[3-({[2-(phenyloxy)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; CDCl₃): 8.62 (s, 1H); 8.35 (m, 1H); 7.98(m, 2H); 7.72(d, 1H); 7.54 (t, 1H); 7.3 (m, 1H); 6.92 (m, 2H); 6.75 (m, 1H); 4.2 (m,2H); 3.97 (m, 2H); 3.0 (s, 3H); MS (EI) for C₂₁H₂₁N₅O₃: 392 (MH⁺)

3-amino-N-methyl-6-{3-[({2-[4-(phenylmethyl)piperazin-1-yl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₂₆H₃₁N₇O₃: 473(MH⁺)

3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)piperidin-4-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz; CDCl₃): 8.62 (s, 1H); 8.35 (m, 1H); 7.98 (m, 2H); 7.68(d, 1H); 7.54 (t, 1H); 7.3 (m, 5H); 6.25 (m, 1H); 3.5 (s, 2H); 3.4 (t,2H); 3.05 (d, 3H); 2.92 (m, 2H); 1.98 (m, 2H); 1.78 (m, 2H); 1.38(m,2H); MS (EI) for C₂₆H₃₀N₆O₂: 459 (MH⁺)

3-amino-6-(3-{[(furan-3-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; CDCl₃): 8.95 (m, 1H); 8.90 (s, 1H); 8.84 (m, 1H); 8.48(s, 1H); 8.35 (d, 1H); 7.83 (d, 1H); 7.6(m, 3H); 6.5 (s, 1H); 4.38 (d,2H); 3.05 (d, 3H); 2.85 (d, 3H); MS (EI) for C₁₈H₁₇N₅O₃: 352 (MH⁺)

3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₂H₂₁N₅O₄: 420 (MH⁺)

3-amino-6-(3-{[(furan-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; CDCl₃): 9.05 (t, 1H); 8.88 (s, 1H); 8.82 (m, 1H); 8.48(s, 1H); 8.38 (d, 1H); 7.85 (d, 1H); 7.55 (m, 2H); 6.39 (m, 1H); 6.35(d, 1H); 3.5 (d, 2H); 2.85 (d, 3H); MS (EI) for C₁₈H₁₇N₅O₃: 352 (MH⁺)

3-amino-N-methyl-6-{3-[({[4-(phenylmethyl)morpholin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₂₅H₂₈N₆O₃: 461(MH⁺)

3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₂H₂₁N₅O₂: 420 (MH⁺)

3-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.07 (t, 1H); 8.88 (s, 1H); 8.85 (m, 1H);8.52 (s, 1H); 8.38 (d, 1H); 7.88 (d, 1H); 7.58 (t, 1H); 7.58 (t, 1H);8.88 (s, 7.08 (d, 1H); 6.7 (d, 1H); 4.5 (m, 2H); 3.2 (m, 2H); 2.85 (d,3H); MS (EI) for C₂₂H₂₁N₅O₃: 404 (MH⁺)

3-amino-6-[3-({[(6-fluoro-4H-1,3-benzodioxin-8-yl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine:MS (EI) for C₂₂H₂₀N₅O₄F: 438 (MH⁺)

3-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.1 (t, 1H); 8.91 (s, 1H); 8.82(m, 1H); 8.52(m, 1H); 8.39 (d, 1H); 7.88 (d, 1H); 7.58(t, 1H); 6.52 (m, 2H); 6.38 (m,1H); 4.48 (d, 2H); 3.76 (s, 6H); 2.85 (d, 3H); MS (EI) for C₂₂H₂₃N₅O₄;422 (MH⁺)

3-amino-N-methyl-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.39 (t, 1H); 8.31 (s, 1H); 8.72 (m, 1H);8.52 (s, 1H); 8.39 (d, 1H); 7.88-7.6 (m, 8H); 4.6 (d, 2H); 3.2 (s, 3H);2.85 (d, 3H); MS (EI) for C₂₁H₂₁N₅O₄S: 440 (MH⁺)

3-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.19 (t, 1H); 8.84 (s, 1H); 8.82 (m, 1H);8.52 (m, 1H); 8.38 (d, 1H); 7.86 (d, 1H); 7.54 (m, 2H); 7.5 (m, 3H); 7.2(t, 1H); 4.54 (d, 2H); 2.84 (d, 3H); MS (EI) for C₂₀H₁₇N₅O₂FBr: 460(MH⁺)

3-amino-6-[3-({[(3-bromo4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.29 (t, 1H); 8.91 (s, 1H); 8.84 (m, 1H);8.52 (s, 1H, 8.39 (d, 1H); 7.88 (d, 1H); 7.58 (t, 1H); 7.4 (m, 1H); 7.35(t, 1H); 4.48 (d, 2H); 2.85 (d, 3H); MS (EI) for C₂₀H₁₇N₅O₂FBr: 458(MH⁺)

3-amino-N-methyl-6-{3-[({[2,4,6-tris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.88 (s, 1H); 8.84 (m, 1H); 8.42(s, 1H); 8.3(d, 1H); 8.18 (m, 1H); 7.88 (d, 1H); 7.5 (t, 1H); 6.2 (s, 2H); 4.4 (d,2H); 3.8 (s, 9H); 2.85(d, 3H); MS (EI) for C₂₃H₂₅N₅O₅: 452 (MH⁺)

3-amino-N-methyl-6-[3-({[(3-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.1 (t, 1H); 8.91 (s, 1H); 8.84 (m, 1H); 8.54(s, 1H); 8.39 (d, 1H); 7.88 (d, 1H); 7.59 (t, 1H); 7.26-7.05 (m, 4H);4.5 (d, 2H); 2.85 (d, 3H); 2.35 (s, 3H); MS (EI) for C₂₁H₂₁N₅O₂:376(MH⁺)

3-amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.18 (t, 1H); 8.92 (s, 1H); 8.84 (m, 1H);8.56 (s, 1H); 8.39 (d, 1H); 7.88 (d, 1H); 7.59 (m, 2H); 7.4 (m, 2H); 4.5(d, 2H); 2.85 (t, 3H); MS (EI) for C₂₀H₁₇N₅O₂FBr: 460 (MH⁺)

3-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.98 (t, 1H); 8.91 (s, 1H); 8.84 (m, 1H);8.54 (s, 1H); 8.39 (d, 1H); 7.88 (d, 1H); 7.59 (t, 1H); 7.5 (m, 2H);7.18 (d, 1H); 4.5 (d, 2H); 2.85 (d, 3H); 2.3 (s, 3H); 2.2 (s, 3H); MS(EI) for C₂₂H₂₃N₅O₂: 390 (MH⁺)

3-amino-6-{3-[({[3,5-bis(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.3 (t, 1H); 8.91 (s, 1H); 8.84 (m, 1H); 8.54(s, 1H); 8.39 (d, 1H); 8.05 (m, 3H); 7.85 (d, 1H); 7.6 (t, 2H); 4.7 (d,2H); 2.85 (d, 3H); MS (EI) for C₂₂H₁₇N₅O₂F6: 498 (MH⁺)

3-amino-6-(3-{[(2,2-diphenylethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.2 (s, 1H); 8.15 (t, 1H); 8.64 (m, 1H); 8.34(m, 2H); 7.7 (d, 1H); 7.5 (t, 1H); 7.39-7.21 (m, 10H); 7.2 (m, 2H); 4.46(t, 1H); 3.95 (m, 2H); 2.85 (d, 3H); MS (EI) for C₂₇H₂₅N₅O₂: 452 (MH⁺)

3-amino-6-[3-({[(4-ethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:(400 MHz; DMSO-D₆): 9.8 (t, 1H); 8.88 (s, 1H); 8.82 (m, 1H); 8.5 (s,1H); 8.36 (d, 1H); 7.86 (d, 1H); 7.56 (t, 2H); 7.25-7.14 (m, 4H); 4.4(d, 2H); 2.85 (d, 3H); 2.6 (m, 2H); MS (EI) for C₂₂₂H₂₃N₅O₂: 390 (MH⁺)

3-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:(400 MHz; DMSO-D₆): 9.08 (t, 1H); 8.88 (s, 1H); 8.81 (m, 1H); 8.5 (s,1H); 8.38 (d, 1H); 7.86 (d, 1H); 7.55 (t, 1H); 7.18 (m, 4H); 4.5 (d,2H); 2.85 (d, 3H); 2.55 (m, 2H); 1.5 (m, 2H); 1.08 (t, 3H); MS (EI) forC₂₃H₂₅N₅O₂: 404 (MH⁺).

3-amino-6-(3-{[(1,1-dimethylethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.92 (s, 1H), 8.88 (m, 1H), 8.38 (m, 2H), (m,2H), 7.90 (m, 1H), 7.81 (m, 1H), 7.71 (br s, 2H), 7.53 (m, 1H), 2.87 (d,3H), 1.43 (s, 9H); MS (EI) for C₁₇H₂₁N₅O₂: 328.5 (MH⁺).

3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.97 (m, 1H), 8.87 (m, 1H), 8.62 (m, 2H),8.41 (m, 1H), 7.96 (m, 1H), 7.74 (br s, 2H), 7.59 (m, 1H), 7.26 (m, 4H),5.52 (m, 1H), 5.14 (m, 1H), 4.55 (m, 1H), 3.14 (m, 1H), 2.93 (m, 1H),2.85 (m, 3H); MS (EI) for C₂₂H₂₁N₅O₃: 404.5 (MH⁺).

3-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.97 (m, 1H), 8.87 (m, 1H), 8.62 (m, 2H),8.41 (m, 1H), 7.96 (m, 1H), 7.74 (br s, 2H), 7.59 (m, 1H), 7.26 (m, 4H),5.52 (m, 1H), 5.14 (m, 1H), 4.55 (m, 3.14 (m, 1H), 2.93 (m, 1H), 2.85(m, 3H); MS (EI) for C₂₂H₂₁N₅O₃: 404.5 (MH⁺).

3-amino-N-methyl-6-{3-[(phenylamino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.34 (m, 1H), 8.97 (s, 1H), 8.90 (m, 1H),8.61 (m, 1H), 8.42 (m, 1H), 7.93 (m, 1H), 7.81 (m, 2H), 7.70 (br s, 2H),7.63 (m, 1H), 7.38 (m, 2H), 7.13 (m, 1H), 2.87 (m, 3H); MS (EI) forC₁₉H₁₇N₅O₂: 348.4 (MH⁺).

3-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.92 (s, 1H), 8.86 (m, 1H), 8.33 (m, 2H),7.67 (br s, 2H), 7.56 (m, 2H), 7.43 (m, 1H), 7.29 (m, 3H), 4.91 (s, 2H),4.79 (s, 2H), 2.84 (m, 3H); MS (EI) for C₂₁H₁₉N₅O₂: 374.5 (MH⁺).

3-amino-N-methyl-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.86 (m, 2H), 8.48 (s, 1H),8.36 (m, 1H), 7.84 (m, 1H), 7.71 (br s, 2H), 7.54 (m, 1H), 7.40 (m, 2H),7.32 (m, 2H), 7.21 (s, 1H), 5.20 (m, 1H), 2.85 (s, 3H), 1.53 (d, 3H); MS(EI) for C₂₁H₂₁N₅O₂; 376.5 (MH⁺).

3-amino-N-methyl-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹l H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.86 (m, 2H), 8.48 (s, 1H),7.21 (s, 1H), 5.20 (m, 1H), 2.85 (s, 3H), 1.53 (d, 3H); MS (EI) forC₂₁H₂₁N₅O₂: 376.5 (MH⁺)

3-amino-N-methyl-6-[3-({[(1R)-1-phenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.83 (m, 2H), 8.47 (s, 1H),8.36 (m, 1H), 7.83 (m, 1H), 7.71 (br s, 2H), 7.54 (t, 1H), 7.39 (m, 2H),7.32 (m, 2H), 7.21 (m, 1H), 4.94 (m, 1H), 2.85 (s, 3H), 1.86 (m, 2H),0.94 (m, 3H); MS (EI) for C₂₂H₂₃N₅O₂: 390.5 (MH⁺).

3-amino-N-methyl-6-[3-({[(1S)-1-phenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.83 (m, 2H), 8.47 (s, 1H),8.36 (m, 1H), 7.83 (m, 1H), 7.71 (br s, 2H), 7.54 (t, 1H), 7.39 (m, 2H),7.32 (m, 2H), 7.21 (m, 1H), 4.94 (m, 1H), 2.85 (s, 3H), 1.86 (m, 2H),0.94 (m, 3H); MS (EI) for

3-amino-N-methyl-6-[3-({[(1R,2S)-2-phenylcyclopropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MH, d₆-DMSO): 8.89 (s, 1H), 8.83 (m, 1H), 8.76 (d, 1H), 8.44(s, 1H), 8.34 (d, 1H), 7.81 (d, 1H), 7.72 (br s, 2H), 7.54 (t, 1H), 7.27(m, 2H), 7.17 (m, 3H), 3.06 (m, 1H), 2.85 (d, 3H), 2.12 (m, 1H), 1.39(m, 1H), 1.26 (m, 1H); MS (EI) for C₂₂H₂₁N₅O₂: 388.5 (MH⁺).

3-amino-N-methyl-6-(3-{[(1R)-1,2,3,4-tetrahydronaphthalen-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.88 (s, 1H), 8.84 (m, 2H), 8.50 (s, 1H),8.38 (d, 1H), 7.90 (d, 1H), 7.71 (brs, 2H), 7.56 (t, 1H), 7.22 (m, 1H),7.16 (m, 3H), 5.29 (m, 1H), 2.84 (d, 3H), 2.79 (m, 2H), 2.02 (m, 2H),1.84 (m, 2H); MS (EI) for C₂₃H₂₃N₅O₂: 402.5 (MH⁺)

3-amino-N-methyl-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, 6-DMSO): 8.88 (s, 1H), 8.84 (m, 2H), 8.50 (s, 1H), 8.38(d, 1H), 7.90 (d, 1H), 7.71 (brs, 2H), 7.56 (t, 1H), 7.22 (m, 1H), 7.16(m, 3H), 5.29 (m, 1H), 2.84 (d, 3H), 2.79 (m, 2H), 2.02 (m, 2H), 1.84(m, 2H); MS (EI) for C₂₃H₂₃N₅O₂: 402.5 (MH⁺).

3-amino-N-methyl-6-{3-[({[3,4,5-tris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.05 (s, 1H), 8.89 (s, 1H), 8.82 (m, 1H),8.50 (s, 1H), 8.36 (d, 1H), 7.87 (d, 1H), 7.71 (br s, 2H), 7.56 (m, 1H),6.67 (s, 2H), 4.45 (s, 2H), 3.76 (s, 6H), 3.62 (s, 3H), 2.84 (s, 3H); MS(EI) for C₂₃H₂₅N₅O₅: 452.5 (MH⁺).

3-amino-N-methyl-6-{3-[({(1R,2R)-2-[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.89 (s, 1H), 8.82 (m, 1H), 8.42 (m, 2H),8.34 (d, 1H), 7.81 (m, 1H), 7.75 (br s, 2H), 7.55 (m, 1H), 7.30 (m, 4H),7.23 (m, 1H), 4.57 (dd, 2H), 4.32 (m, 1H), 3.94 (m, 1H), 2.83 (d, 3H),2.07 (m, 1H), 1.95 (m, 1H), 1.70 (m, 4H); MS (EI) for C₂₅H₂₇N₅O₃: 446.6(MH⁺).

3-amino-N-methyl-6-{3-[({(1S,2S)-2-[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.89 (s, 1H, 8.82 (m, 1H), 8.42 (m, 2H), 8.34(d, 1H), 7.81 (m, 1H, 7.75 (br s, 2H), 7.55 (m, 1H), 7.30 (m, 4H, 7.23(m, 1H), 4.57 (dd, 2H), 4.32 (m, 1H, 3.94 (m, 1H, 2.83 (d, 3H), 2.07 (m,1H), 1.95 (m, 1H), 1.70 (m, 4H); MS (EI) for C₂₅H₂₇N₅O₃: 446.5 (MH⁺).

3-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.02 (t, 1H, 8.90 (s, 1H), 8.84 (m, 1H), 8.49(s, 1H), 8.38 (d, 1H), 7.86 (d, 1H), 7.74 (br s, 2H), 7.56 (t, 1H), 7.47(m, 5H), 7.38 (m, 3H), 7.26 (m, 1H), 4.49 (d, 2H), 2.85 (d, 3H); MS (EI)for C₂₆H₂₃N₅O₂: 438.5 (MH⁺).

3-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.19 (t, 1H), 8.92 (s, 1H), 8.84 (m, 1H, 8.55(s, 1H), 8.40 (d, 1H), 7.91 (d, 1H), 7.75 (br s, 2H), 7.65 (m, 4H, 7.59(t, 1H), 7.46 (m, 4H), 7.35 (m, 1H), 4.58 (d, 2H), 2.86 (d, 3H); MS (EI)for C₂₆H₂₃N₅O₂: 438.5 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.14 (t, 1H, 8.91 (s, 1H), 8.84 (m, 1H), 8.54(s, 1H), 8.39 (d, 1H), 7.89 (d, 1H), 7.75 (br s, 2H), 7.58 (t, 1H), 7.38(m, 4H), 7.12 (m, 1H), 6.99 (m, 4H), 2.87 (d, 3H),; MS (EI) forC₂₆H₂₃N₅O₃: 454.5 (MH⁺).

3-amino-N-methyl-6-{3-[({[3-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 M, d₆-DMSO): 9.14 (t, 1H), 8.90 (s, 1H), 8.83 (m, 1H), 8.51(s, 1H), 8.39 (d, 1H), 7.86 (d, 1H), 7.74 (br s, 2H), 7.57 (t, 1H), 7.37(m, 3H), 7.13 (m, 2H), 7.01 (m, 3H), 6.88 (m, 1H), 4.52 (d, 2H), 2.86(d, 3H); (d, 3H); MS (EI) for C₂₆H₂₃N₅O₃: 454.6 (MH⁺)

3-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.19 (t, 1H), 8.92 (s, 1H), 8.84 (m, 1H),8.56 (s, 1H), 8.39 (d, 1H), 7.90 (d, 1H), 7.69 (br s, 2H), 7.65 (m, 3H),7.57 (m, 2H), 7.46 (m, 3H), 7.38 (m, 2H), 4.63 (d, 2H), 2.83 (d, 3H); MS(EI) for C₂₆H₂₃N₅O₂: 438.4 (MH⁺).

3-amino-N-methyl-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.96 (s, 1H), 8.87 (m, 1H), 8.54 (s, 1H),8.48 (s, 1H), 8.38 (d, 1H), 7.82 (d, 1H), 7.75 (br s, 2H), 7.55 (t, 1H),7.42 (m, 2H), 7.30 (m, 2H), 7.18 (m, 1H), 2.85 (d, 3H), 1.71 (s, 6H); MS(EI) for C₂₂H₂₃N₅O₂: 390.4 (MH⁺).

3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.13 (t, 1H), 8.91 (s, 1H), 8.84 (m, 1H),8.52 (s, 1H), 8.40 (d, 1H), 7.87 (d, 1H), 7.73 (br s, 2H), 7.58 (t, 1H),7.48 (m, 1H), 7.25 (m, 1H), 7.08 (m, 1H), 4.53 (d, 2H), 2.85 (d, 3H); MS(EI) for C₂₀H₁₇N₅O₂F₂: 398.3 (MH⁺).

3-amino-6-{3-[({[2-chloro-6-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.85 (s, 1H), 8.83 (m, 1H), 8.69 (t, 1H),8.36 (s, 1H), 8.33 (d, 1H), 7.77 (d, 1H), 7.72 (br s, 2H), 7.51 (t, 1H),7.34 (m, 4H), 7.05 (m, 3H), 6.85 (d, 1H), 4.67 (d, 2H), 2.83 (d, 3H); MS(EI) for C₂₆H₂₂N₅O₃Cl: 488.4 (MH⁺).

3-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.18 (t, 1H), 8.92 (s, 1H), 8.84 (m, 1H),8.56 (s, 1H), 8.41 (d, 1H), 7.91 (d, 1H), 7.74 (br s, 2H), 7.60 (t, 1H),7.54 (d, 1H), 7.41 (m, 2H), 4.58 (d, 2H), 2.86 (d, 3H); MS (EI) forC₂₀H₁₇N₅O₂Cl₂: 430.4 (MH⁺).

3-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.90 (s, 1H), 8.86 (m, 1), 8.45 (s, 1H), 8.33(d, 1H), 8.28 (t, 1H), 7.84 l (d, 1H), 7.71 (br s, 2H), 7.53 (t, 1H),7.27 (t, 1H), 6.69 (d, 2H), 4.50 (d, 2H), 3.80 (s, 6H), 2.85 (d, 3H); MS(EI) for C₂₂H₂₃N₅O₄: 422.4 (MH⁺).

3-amino-6-[3-({[(2-chloro-6-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.89 (s, 1H), 8.84 (m, 1H), 8.69 (m, 1H),8.47 (s, 1H), 8.36 (d, 1H), 7.85 (d, 1H), 7.69 (br s, 2H), 7.54 (t, 1H),7.32 (m, 1H), 7.24 (m, 2H), 4.65 (d, 2H), 2.85 (d, 3H), 2.45 (s, 3H); MS(EI) for C₂₁H₂₀N₅O₂Cl: 410.4 (MH⁺).

3-amino-N-methyl-6-[3-({[(2,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.14 (t, 1H), 8.92 (s, 1H), 8.85 (m, 1H),8.53 (s, 1H), 8.40 (d, 1H), 7.87 (d, 1H), 7.75 (br s, 2H), 7.58 (m, 2H),7.50 (m, 1H), 4.52 (d, 2H), 2.86 (d, 3H); MS (EI) for C₂₀H₁₆N₅O₂F₃:416.4 (MH⁺).

3-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.22 (t, 1H), 8.93 (s, 1H), 8.86 (m, 1H),8.57 (s, 1H), 8.42 (d, 1H), 7.90 (d, 1H), 7.76 (br s, 2H), 7.60 (m, 2H),7.39 (m, 2H), 4.62 (d, 2H), 2.86 (d, 3H); MS (EI) for C₂₀H₁₇N₅O₂Cl₂:430.32 (MH⁺).

3-amino-6-[3({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.16 (t, 1H), 8.91 (s, 1H), 8.84 (m, 1H),8.53 (s, 1H), 8.40 (d, 1H), 7.87 (d, 1H), 7.80 (br s, 2H), 7.58 (t, 1H),7.45 (m, 2H), 7.29 (d, 1H), 4.53 (d, 2H), 2.86 (d, 3H); MS (EI) forC₂₀H₁₇N₅O₂FCl: 414.4 (NH⁺).

3-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.21 (t, 1H), 8.92 (s, 1H), 8.85 (m, 1H),8.54 (s, 1H), 8.40 (d, 1H), 7.88 (d, 1H), 7.73 (br s, 2H), 7.59 (t, 1H),7.52 (m, 1H), 7.42 (m, 2H), 4.54 (d, 2H), 2.86 (d, 3H); MS (EI) forC₂₀H₁₇N₅O₂Cl₂: 403.3 (MH⁺).

3-amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.17 (t, 1H), 8.92 (s, 1H), 8.86 (m, 1h),8.54 (s, 1H), 8.41 (d, 1H), 7.89 (d, 1H), 7.77 (br s, 2H), 7.59 (t, 1H),7.46 (m, 1H), 7.41 (m, 1H), 7.28 (m, 1H), 4.55 (d, 2H), 2.86 (d, 3H); MS(EI) for C₂₀H₁₇N₅O₂FCl: 414.4 (MH⁺).

3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.21 (t, 1H), 8.91 (s, 1H), 8.85 (m, 1H),8.53 (s, 1H), 8.40 (d, 1H), 7.88 (d, 1H), 7.72 (br s, 2H), 7.60 (m, 3H),7.36 (d, 1H), 4.53 (d, 2H), 2.86 (d, 3H); MS (EI) for C₂₀H₁₇N₅O₂Cl₂:430.3 (MH⁺).

3-amino-6-[3-({[(4′-fluorobiphenyl-2-yl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.03 (t, 1H), 8.90 (s, 1H), 8.84 (m, 1H),8.49 (s, 1H), 8.38 (d, 1H), 7.85 (d, 1h), 7.71 (br s, 2H), 7.56 (t, 1H),7.49 (m, 3H), 7.42-7.22 (m, 5H), 4.46 (d, 2H), 2.86 (d, 3H); MS (EI) forC₂₆H₂₂N₅O₂F; 456.4 (MH⁺).

3-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): (9.12 (t, 1H), 8.91 (s, 1H), 8.84 (m, 1H),8.53 (s, 1H), 8.39 (d, 1H), 7.89 (d, 1H), 7.73 (br s, 2H), 7.58 (t, 1H),7.26 (m, 1H), 7.20 (m, 1H), 7.10 (m, 1H), 4.48 (d, 2H), 2.85 (d, 3H),2.23 (s, 3H); MS (EI) for C₂₁H₂₀N₅O₂F: 394.4 (MH⁺).

3-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.19 (t, 1H), 8.92 (s, 1H), 8.84 (m, 1H),8.54 (s, 1H), 8.40 (d, 1H), 7.88 (d, 1H), 7.76 (br s, 2H), 7.58 (t, 1H),7.51 (t, 1H), 7.41 (t, 1H), 7.22 (t, 1H), 4.60 (d, 2H), 2.86 (d, 3H); MS(EI) for C₂₀H₁₇N₅O₂FCl: 414.4 (MH⁺).

3-amino-6-[3-({[(6-chloro-2-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.89 (s, 1H), 8.84 (m, 1H), 8.48 (s, 1H),8.37 (d, 2H), 7.85 (d, 1H), 7.74 (br s, 2H), 7.55 (t, 1H), 7.27 (m, 2H),4.64 (d, 2H), 2.85 (d, 3H), 2.24 (s, 3H); MS (EI) for C₂₁H₁₉N₅O₂FCl:428.4 (MH⁺).

3-amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.17 (t, 1H), 8.91 (s, 1H, 8.84 (m, 1H), 8.52(s, 1H), 8.39 (d, 1H), 7.88 (d, 1H), 7.74 (br s, 7.71 (d, 2H), 7.58 (t,1H), 7.18 (d, 2H), 4.49 (d, 2H), 2.86 (d, 3H); MS (EI) for C₂₀H₁₈N₅O₂I:488.2 (MH⁺).

3-amino-6-[3-({[(3-chloro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.16 (t, 1H), 8.92 (s, 1H), 8.85 (m, 1H),8.53 (s, 1H), 8.39 (d, 1H), 7.88 (d, 1H), 7.75 (br s, 2H), 7.58 (t, 1H),7.39 (s, 1H), 7.32 (d, 1H), 7.23 (d, 1H), 4.49 (d, 2H), 2.87 (d, 3H),2.31 (s, 3H); MS (EI) for C₂₁H₂₀N₅O₂Cl: 410.4 (MH⁺).

3-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.13 (t, 1H), 8.89 (s, 1H), 8.82 (m, 1H),8.52 (s, 1H), 8.38 (d, 1H), 7.86 (d, 1H), 7.71 (br s, 2H), 7.56 (t, 1H),7.31-7.10 (m, 3H), 4.55 (d, 2H), 2.85 (d, 3H); MS (EI) for C₂₀H₁₇N₅O₂F₂:398.5 (MH⁺).

3-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.95 (t, 1H), 8.86 (s, 1H), 8.80 (m, 1H),8.45 (s, 1H), 8.34 (d, 1H), 7.81 (d, 1H), 7.71 (br s, 2H), 7.53 (t, 1H),7.38 (m, 1H), 7.09 (m, 1H), 4.56 (d, 2H), 2.84 (d, 3H); MS (EI) forC₂₀H₁₇N₅O₂F₂: 398.4 (MH⁺).

3-amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.18 (t, 1M), 8.89 (s, 1H), 8.82 (m, 1H),8.52 (s, 1h), 8.37 (d, 1H), 7.86 (d, 1H), 7.71 (br s, 2H), 7.56 (t, 1H),7.15-7.01 (m, 3H), 4.54 (d, 2H), 2.86 (d, 3H); MS (EI) for C₂₀H₁₇N₅O₂F₂:398.5 (MH⁺).

3-amino-6-[3-({[(3-iodophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.14 (t, 1H), 8.88 (s, 1H), 8.82 (m, 1H),8.50 (s, 1h), 8.37 (d, 1H), 7.86 (d, 1H), 7.71 (br s, 1H), 7.67 (br s,2H), 7.64-7.52 (m, 2H), 7.36 (d, 1H), 7.14 (t, 1H), 4.48 (d, 2H), 2.86(d, 3H); MS (EI) for C₂₀H₁₈N₅O₂I: 488.4 (MH⁺).

3-amino-N-methyl-6-[3-({[(2-piperidin-1-ylphenyl)methyl]amino}carbonyl)phenyl[pyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.63 (s, 1H), 8.36 (m, 1H), 8.11 (m, 1H), 7.95(m, 2H), 7.72 (d, 1H), 7.50 (t, 1H), 7.32 (m, 1H), 7.26 (m, 1h), 7.16(d, 1H), 7.08 (t, 1H), 4.78 (d, 2H), 3.02 (d, 3H), 2.92 (m, 4H),1.78-1.49 (m, 6H); MS (EI) for C₂₅H₂₈N₆O₂: 445.5 (MH⁺).

3-amino-N-methyl-6-{3-[({[2-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.04 (t, 1H), 8.90 (s, 1H), 8.82 (m, 1H),8.54 (m, 1H), 8.38 (d, 1H), 7.88 (d, 1H), 7.70 (br s, 2H), 7.57 (t, 1H),7.28 (m, 3H), 7.15 (m, 1H), 4.52 (d, 2H), 2.85 (d, 3H), 2.51 (s, 3H); MS(EI) for C₂₁H₂₁N₅O₂S: 408.4 (MH⁺).

3-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.15 (t, 1H), 8.92 (s, 1H), 8.85 (m, 1H),8.56 (m, 1H), 8.41 (d, 1H), 7.89 (d, 1H), 7.73 (br s, 2H), 7.59 (t, 1H),7.48 (m, 2H), 7.24 (m, 1H), 4.57 (d, 2H), 2.85 (d, 3H); MS (EI) forC₂₀H₁₇N₅O₂FCl: 414.4 (MH⁺).

3-amino-6-{3-[({(3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.05 (t, 1H), 8.91 (s, 1H), 8.84 (m, 1H),8.52 (m, 1H), 8.37 (d, 1H), 7.88 (d, 1H), 7.74 (br s, 2H), 7.57 (t, 1H),6.98 (m, 1H), 6.89 (m, 2H), 4.47 (d, 2H), 3.74 (s, 3H), 3.73 (s, 3),2.85 (d, 3H); MS (EI) for C₂₂H₂₃N₅O₄: 422.5 (MH⁺).

3-amino-N-methyl-6-{3-[(phenylmethyl)amino]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.65 (s, 1H), 8.60 (m, 1H), 7.58 (br s, 2H),7.42 (m, 1H), 7.37-7.19 (m, 6H), 7.13 (t, 1H), 6.60 (d, 1H), 6.23 (m,1H), 4.57 (d, 2H), 2.85 (d, 3H); MS (EI) for C₁₉H₁₉N₅O: 334.4 (MH⁺).

3-amino-6-[3-({[(2-amino-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, (4-DMSO): 9.01 (t, 1H), 8.88 (s, 1H), 8.82 (m, 1H),8.48 (s, 1H), 8.36 (d, 1H), 7.86 (d, 1H), 7.71 (br s, 2H), 7.54 (t, 1H),6.96 (m, 1H), 6.45 (d, 1H), 6.32 (t, 1H), 5.66 (s, 2H), 4.45 (d, 2H),2.84 (d, 3H); MS (EI) for C₂₀H₁₉N₆O₂F: 395.4 (MH⁺).

3-amino-6-{3-[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.23 (t, 1H), 8.93 (s, 1H), 8.84 (m, 1H),8.57 (m, 1H), 8.42 (d, 1H), 7.91 (d, 1H), 7.76 (br s, 2H), 7.69-7.52 (m,4H), 4.68 (d, 2H), 2.85 (d, 3H); MS (EI) for C₂₁H₁₇N₅O₂F₄: 448.4 (MH⁺).

3-amino-N-methyl-6-{3-[({[6-(trifluoromethyl)pyridin-3-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide: ¹H NMR (400 MHz, d₆-DMSO): 9.29(t, 1H), 8.91 (s, 1H), 8.85 (m, 1H), 8.79 (s, 1H), 8.54 (s, 1H), 8.40(d, 1H), 8.05 (d, 1H), 7.89 (m, 2H), 7.76 (br s, 2H), 7.59 (t, 1H), 4.65(d, 2H), 2.85 (d, 3H); MS (EI) for C₂₀H₁₇N₆O₂F₃: 431.4 (MH⁺).

3-amino-6-(3-{[2-(2,5-difluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹ H NMR (400 MHz, d₆-DMSO): 10.52 (s, 1H), 8.93 (s, 1H), 8.84 (m, 1H),8.59 (s, 1H), 8.42 (d, 1H), 8.20 (s, 1H), 7.88 (d, 1H), 7.74 (br s, 2H),7.60 (t, 1H), 7.15 (m, 1H), 6.63 (m, 1H), 6.51 (m, 1H), 2.86 (d, 3H); MS(EI) for C₁₉H₁₆N₆O₂F₂: 399.4 (MH⁺).

3-amino-N-methyl-6-(3-{[2-(2,3,5,6-tetrafluoro-4-methylphenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.76 (s, 1H), 8.88 (s, 1H), 8.81 (m, 1H),8.50 (s, 1H), 8.39 (d, 1H), 8.19 (s, 1H), 7.83 (d, 1H), 7.73 (br s, 2H),7.57 (t, 1H), 2.87 (d, 3H), 2.15 (s, 3H); MS (EI) for C₂₀H₁₆N₆O₂F₄:449.4 (MH⁺).

3-amino-6-(3-{[2-(2-fluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.50 (s, 1H), 8.92 (s, 1H), 8.84 (m, 1H),8.58 (s, 1H), 8.41 (d, 1H), 7.88 (m, 2H), 7.74 (br s, 2H), 7.60 (t, 1H),7.10 (m, 1H), 6.98 (m, 1H), 6.88 (m, 1H), 6.75 (m, 1H), 2.86 (d, 3H); MS(EI) for C₁₉H₁₇N₆O₂F: 381.4 (MH⁺).

3-amino-6-(3-{[2-(2,4-difluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.51 (s, 1H), 8.91 (s, 1H), 8.84 (m, 1H),8.57 (s, 1H), 8.41 (d, 1H), 7.85 (m, 2H), 7.74 (br s, 2H), 7.59 (t, 1H),7.17 (m, 1H), 6.89 (m, 2H), 2.87 (d, 3H); MS (EI) for C₁₉H₁₆N₆O₂F₂:399.4 (MH⁺).

3-amino-N-methyl-6-(3-{[2-(2,3,5,6-tetrafluorophenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.80 (s, 1H), 8.88 (s, 1H), 8.81 (m, 1H),8.50 (s, 1H), 8.40 (m, 2H), 7.84 (d, 1H), 7.73 (br s, 2H), 7.58 (t, 1H),7.20 (m, 1H), 2.87 (d, 3H); MS (EI) for C₁₉H₁₄N₆O₂F₄: 435.4 (MH⁺).

3-Amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.08 (t, 1H), 8.91 (s, 1H), 8.84 (q, 1H),8.54-8.52 (m, 1H), 8.39 (d, 1H), 7.58 (t, 1H), 6.95 (s, 2H), 6.88 (s,1H), 4.46 (d, 2H), 4.10-3.70 (m, 2H), 2.85 (d, 3H), 2.25 (s, 6H); MS(EI) for C₂₂H₂₃N₅O₂: 390 MH⁺).

3-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.06 (t, 1H), 8.91 (s, 1H), 8.84 (q, 1H),8.56-8.53 (m, 1H), 8.40 (d, 1H), 8.00-7.30 (m, 2H), (m, 7.90 (d, 1H),7.59 (t, 1H), 7.29 (s, 1H) 7.24-7.22 (m, 2H), 4.50 (d, 2H), 2.86 (d,3H), 2.34 (s, 3H); MS (EI) for C₂₁H₂₀N₅O₂Cl: 410 (MH⁺).

3-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.96 (t, 1H), 8.91 (s, 1H), 8.85 (q, 1H),8.54-8.52 (m, 1H), 8.39 (d, 1H), 7.89 (d, 1H), 7.58 (t, 1H), 7.17 (d,1H), 7.02-6.95 (m, 2H), 4.46 (d, 2H), 4.00-3.30 (m, 2), 2.85 (d, 3H),2.31 (s, 3H), 2.25 (s, 3H); MS (EI) for C₂₂H₂₃N₅O₂: 390 (MH⁺).

3-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MH, d₆-DMSO): 9.20 (t, 1H), 8.92 (s, 1H), 8.85 (q, 1H),8.55-8.52 (m, 1H), 8.40 (d, 1H), 7.88 (d, 1H), 7.58 (t, 1H), 7.40-7.30(m, 1H), 7.28-7.16 (m, 2H), 4.60 (d, 2H), 4.20-3.80 (m, 2H), 2.85 (d,3H); MS (EI) for C₂₀H₁₇N₅O₂F₂: 398 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.13 (t, 1H), 8.91 (s, 1H), 8.84 (q, 1H),8.53-8.51 (m, 1H), 8.39 (d, 1H), 8.00-7.30 (m, 2H), 7.88 (d, 1H), 7.58(t, 1H), 7.31 (d, 2H), 7.24 (d, 2H), 4.49 (d, 2H), 2.85 (d, 3H), 2.45(s, 3H); MS (EI) for C₂₁H₂₁N₅O₂S: 408 (MH⁺).

3-amino-N-methyl-6-(3-{[(2-methylpropyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.84 (q, 1H), 8.56 (t, 1H),8.48-8.45 (m, 1H), 8.36 (dt, 1H), 8.20-7.30 (m, 2H), 7.83 (dt, 1H), 7.56(t, 1H), 3.13 (dd, 2M), 2.86 (d, 3H), 1.94-1.82 (m, 1H), 0.92 (d, 6H);MS (EI) for C₁₇H₂₁N₅O₂: 328 (MH⁺).

3-amino-N-methyl-6-(3-{[({3-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.24 (t, 1H), 8.91 (s, 1H), 8.85 (q, 1H),8.55-8.53 (m, 1H), 8.40 (d, 1H), 8.20-7.20 (m, 2H), 7.88 (d, 1H), 7.59(t, 1H), 7.49 (t, 1H), 7.40 (d, 1H), 7.35 (s, 1H), 7.26 (d, 1H), 4.58(d, 2H), 2.85 (d, 3H); MS (EI) for C₂₁H₁₈N₅O₃F₃: 446 (MH⁺).

3-amino-6-(3-{[(cyclopropylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.85 (q, 1H), 8.67 (t, 1H),8.49-8.46 (m, 1H), 8.36 (dt, 1H), 8.10-7.20 (m, 2H), 7.85 (dt, 1H), 7.56(t, 1H), 3.19 (dd, 2H), 2.86 (d, 3H), 1.12-1.01 (m, 1H), 0.49-0.43 (m,2H), 0.29-0.23 (m, 2H); MS (EI) for C₁₇H₁₉N₅O₂: 326 (MH⁺).

3-amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.86 (q, 1H), 8.44-8.42 (m,1H), 8.39-8.33 (m, 2H), 8.10-7.20 (m, 2H), 7.82 (dt, 1H), 7.54 (t, 1H),4.31-4.21 (m, 1H), 2.85 (d, 3H), 1.99-1.86 (m, 2H), 1.79-1.66 (m, 2H),1.62-1.50 (m, 4H); MS (EI) for C₁₈H₂₁N₅O₂: 340 (MH⁺).

3-amino-N-methyl-6-(3-{[(4-methylphenyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.3 (s, 1H), 8.95 (s, 1H), 8.89 (q, 1H),8.59-8.57 (m, 1H), 8.40 (d, 1H), 8.00-7.30 (m, 2H), 7.90 (d, 1H), 7.69(d, 2H), 7.62 (t, 1H), 7.18 (d, 2H), 2.86 (d, 3H), 2.30 (s, 3H); MS (EI)for C₂₀H₁₉N₅O₂: 362 (MH⁺).

3-amino-N-methyl-6-[3-({[4-(methyloxy)phenyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 M, d₆-DMSO): 10.2 (s, 1H), 8.95 (s, 1H), 8.89 (q, 1H),8.59-8.57 (m, 1H), 8.40 (dt, 1H), 8.00-7.40 (m, 2H), 7.90 )dt, 1H),7.73-7.68 (m, 2H), 7.61 (t, 1H), 6.98-6.93 (m, 2H), 3.76 (s, 3H), 2.86(d, 3H); MS (EI) for C₂₀H₁₉N₅O₃: 378 (MH⁺).

3-amino-6-(3-{[(2,2-dimethylpropyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.92 (s, 1H), 8.85 (q, 1H), 8.49-8.43 (m,2H), 8.36 (dt, 1H), 8.00-7.40 (m, 2H), 7.83 (dt, 1H), 7.56 (t, 1H), 3.16(d, 2H), 2.85 (d, 3H), 0.93 (s, 9H); MS (EI) for C₁₈H₂₃N₅O₂: 342 (MH⁺).

3-amino-6-(3-{[(cyclopentylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.91 (s, 1H), 8.85 (q, 1H), 8.57 (t, 1H),8.47-8.44 (m, 1H), 8.36 (d, 1H), 8.00-7.30 (m, 2H), 7.82 (d, 1H), 7.55(t, 1H), 3.26-3.21 (m, 2H), 2.86 (d, 3H), 2.23-2.12 (m, 1H), 1.72-1.45(m, 6H), 1.33-1.22 (m, 2H); MS (EI) for C₁₉H₂₃N₅O₂: 354 (MH⁺).

3-amino-6-{3-[(cyclopropylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.90 (s, 1H), 8.85 (q, 1H), 8.55-8.52 (m,1H), 8.43-8.41 (m, 1H), 8.35 (d, 1H), 8.00-7.40 (m, 2H), 7.80 (d, 1H),7.54 (t, 1H), 2.91-2.84 (m, 4H), 0.77-0.57 (m, 4H); MS (EI) forC₁₆H₁₇N₅O₂: 312 (MH⁺).

3-amino-N-methyl-6-[3-({[(2,3,4-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.17 (t, 1H), 8.91 (s, 1H), 8.84 (q, 1H),8.53-8.51 (m, 1H), 8.40 (d, 1H), 8.00-7.40 (m, 2H), 7.86 (d, 1H), 7.58(t, 1H), 7.35-7.27 (m, 2H), 4.56 (d, 2H), 2.85 (d, 3H); MS (EI) forC₂₀H₁₆N₅O₂F₃: 416 (MH⁺).

3-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.05 (t, 1H), 8.89 (s, 1H), 8.83 (q, 1H),8.48-8.46 (m, 1H), 8.37 (d, 1H), 7.90-7.20 (m, 2H), 7.83 (d, 1H),7.66-7.58 (m, 1H), 7.55 (t, 1H), 7.20 (td, 1H), 4.59 (d, 2H), 2.84 (d,3H); MS (EI) for C₂₀H₁₆N₅O₂F₂Cl: 432 (MH⁺).

3-amino-6-{3-[(9H-fluoren-9-ylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.18 (d, 1H), 8.87 (s, 1H), 8.83 (q, 1H),8.57-8.55 (m, 1H), 8.44 (d, 1H), 8.10-7.20 (m, 2H), 8.00 (d, 1H), 7.92(d, 2H), 7.62-7.56 (m, 3H), 7.46 (t, 2H), 7.38-7.32 (m, 2H), 6.34 (d,1H), 2.83 (d, 3H); MS (EI) for C₂₆H₂₁N₅O₂: 436 (MH⁺).

3-amino-N-methyl-6-[3-({[(2-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.01 (t, 1H), 8.91 (s, 1H), 8.83 (q, 1H),8.55-8.53 (m, 1H), 8.39 (d, 1H), 8.00-7.30 (m, 2H), 7.90 (d, 1H), 7.58(t, 1H), 7.32-7.26 (m, 1H), 7.20-7.14 (m, 3H), 4.52 (d, 2H), 2.85 (d,3H); MS (ED for C₂₁H₂₁N₅O₂: 376 (MH⁺).

3-amino-6-(3-({[(3,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.13 (t, 1H), 8.91 (s, 1H), 8.87 (q, 1H),8.56-8.53 (m, 1H), 8.37 (dt, 1H), 8.20-7.30 (m, 2H), 7.88 (dt, 1H), 7.57(t, 1H), 7.14-7.04 (m, 3H), 4.45 (d, 2H), 2.85 (d, 3H), 2.20 (s, 3H),2.19 (s, 3H); MS (EI) for C₂₂H₂₃N₅O₂: 390 (MH⁺).

3-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.07 (t, 1H), 8.92 (s, 1H), 8.85 (q, 1H),8.56-8.54 (m, 1H), 8.40 (d, 1H), 8.00-7.30 (m, 2H), 7.89 (dt, 1H), 7.59(t, 1H, 7.22 (dd, 1H, 7.07 (dd, 1H), 7.00 (td, 1H), 4.49 (d, 2H), 2.85(d, 3H), 2.32 (s, 3H); MS (EI) for C₂₁H₂₀N₅O₂F: 394 (MH⁺).

3-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 M, d₆-DMSO): 9.28 (t, 1H), 8.92 (s, 1H), 8.89 (q, 1H),8.58-8.55 (m, 1H), 8.39 (d, 1H), 8.00-7.30 (m, 2H), 7.88 (d, 1H), 7.58(t, 1H), 7.46-7.36 (m, 2H), 7.24-7.19 (m, 1H), 4.51 (d, 2H), 2.86 (d,3H); MS (EI) for C₂₀H₁₇N₅O₂F₂: 398 (MH⁺).

3-amino-6-[3-({[(2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 M, d₆-DMSO): 9.13 (t, 1H), 8.91 (s, 1H), 8.84 (q, 1H),8.55-8.52 (m, 1H), 8.40 (d, 1H), 8.00-7.10 (m, 2H), 7.89 (d, 1H), 7.58(t, 1H), 7.43 (td, 1H), 7.36-7.29 (m, 1H), 7.24-7.15 (m, 2H), 4.57 (d,2H), 2.86 (d, 3H); MS (EI) for C₂₀H₁₈N₅O₂F: 380 (MH⁺).

3-amino-N-methyl-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.03 (t, 1H), 8.86 (s, 1H), 8.80 (q, 1H),8.45 (t, 1H), 8.35 (dt, 1H), 8.00-7.28 (m, 2H), 7.81 (dt, 1H), 7.81 (dt,1H), 7.53 (t, 1H), 7.50-7.39 (m, 1H), 7.17-7.09 (m, 1H), 4.58 (d, 2H),2.84 (d, 3H); MS (EI) for C₂₀H₁₆N₅O₂F₃: 416 (MH⁺).

3-amino-N-methyl-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.17 (t, 1H), 8.89 (s, 1H), 8.83 (q, 1H),8.51 (t, 1H), 8.37 (dt, 1H), 8.00-7.00 (m, 2H), 7.85 (dt, 1H), 7.56 (t,1H), 7.33-7.25 (m, 2H), 4.50 (d, 2H), 2.85 (d, 3H); MS (EI) forC₂₀H₁₆N₅O₂F₃: 416 (MH⁺).

'3-amino-6-{3-[({[4-aminosulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.24 (t, 1H), 8.92 (s, 1H), 8.84 (q, 1H),8.56 (s, 1H), 8.40 (d, 1H), 7.88 (d, 1H), 7.80 (d, 2H), 7.58 (dd, 1H),7.54 (d, 2H), 7.34 (s, 2H), 4.60 (d, 2H), 2.83 (d, 3H); MS (EI) forC₂₀H₂₀N₆O₄S: 441 (MH⁺).

'3-amino-6-[3-({[(2,3-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.64 (s, 1H), 8.36 (s, 1H), 7.99 (m, 2H), 7.68(d, 1H), 7.51 (dd, 1H), 7.17 (m, 3H), 7.23 (t, 1H), 4.70 (d, 2H), 3.03(d, 3H), 2.35 (s, 3H), 2.29 (s, 3H); MS (EI) for C₂₂H₂₃N₅O₂: 390 (MH⁺).

'3-amino-6-{3-[({[4-hydroxy-3-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-methanol): 8.76 (s, 1H), 8.54 (s, 1H), 8.20 (d, 1H),7.86 (d, 1H), 7.57 (dd, 1H), 6.98 (s, 1H), 6.84 (d, 1H), 6.76 (d, 1H),4.54 (s, 2H), 3.85 (s, 3H), 2.97 (s, 3H); MS (EI) for C₂₁H₂₁N₅O₄: 408(MH⁺).

'3-amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-methanol): 8.76 (s, 1H), 8.55 (s, 1H), 8.22 (d, 1H),7.86 (d, 1H), 7.58 (dd, 1H), 7.29 (d, 1H), 7.23 (s, 1H), 7.17 (d, 1H),4.60 (s, 2H), 2.97 (s, 3H), 2.40 (s, 3H); MS(EI) for C₂₁H₂₀N₅O₂Cl: 410(MH⁺).

'3-amino-6-{3-[({[2-(ethyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d-chloroform): 8.64 (s, 1H), 8.36 (s, 1H), 7.99 (m,2H), 7.68 (d, 1H), 7.51 (dd, 1H), 7.37 (d, 1H), 7.28 (dd, 1H), 6.94 (dd,1H), 6.87 (d, 1H), 6.82 (t, 1H), 4.69 (d, 2H), 4.13 (q, 2H), 3.03 (d,3H), 1.45 (t, 3H); MS(EI) for C₂₂H₂₃N₅O₃: 406 (MH⁺).

3-amino-N-methyl-6-(3-{[(naphtalen-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz; d₆-DMSO): 9.17 (br s, 1H), 8.9(s, 1H), 8.82 (s, 1H), 8.56 (s, 1H), 8.42-8.36 (d, 1H), 8.24-8.18 (d,1H), 8-7.82 (td, 3H), 7.64-7.46 (m, 5H), 5.00 (s, 2H), 2.57 (s, 3H); MS(EI) for C₂₄H₂₁N₅O₂: 412 (MH⁺).

3-amino-N-methyl-6-(3-{[(tetrahydrofuran-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS(EI) for C₁₈H₂₁N₅O₃: 356 (MH⁺).

3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.90 (s, 1H), 8.82 (s, 1H), 8.85 (s, 1H),8.34-8.38 (d, 1H), 7.88-7.80 (d, 1H), 7.60-7.52 (t, 1H), 7.46-7.34 (m,1H), 7.30-7.22 (t, 1H), 4.50 (s, 2H), 2.80 (s, 3H); MS (EI) forC₂₀H₁₇N₅O₂FCl: 414 (MH⁺).

3-amino-6-{3-[({[3-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H N (400 MHz, d₆-DMSO): 9.28 (br s, 1H), 8.90 (s, 1H), 8.82 (s, 1H),8.54 (s, 1H), 8.44-8.36 (d, 2H), 7.94-7.84 (d, 1H), 7.68-7.48 (m, 4H);MS (EI) for C₂₁H₁₇N₅O₂F₄: 448 (MH⁺).

3-amino-6-{3-[({2-[3,5-bis(methyloxy)phenyl]ethyl}amino)carbonyl}phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.90 (s, 1H), 8.84 (d, 1H), 8.64 (s, 1H),8.45 (s, 1H), 8.38-8.34 (d, 1H), 7.86-7.78 (d, 1H), 7.58-7.52 (t, 3H),6.90-6.84 (d, 1H), 6.82-6.78 (d, 1H); MS (EI) for C₂₃H₂₅N₅O₄: 436 (MH⁺).

3-amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz d₆-DMSO): 9.20 (s, 1H), 8.90 (s, 1H), 8.88-8.82 (d, 1H),8.56 (s, 1H), 8.40-8.32 (d, 1H), 7.90-7.80 (d, 1H), 7.60-7.50 (t, 1H),6.95 (s, 1H), 6.90-6.78 (q, 2H), 6.00 (s, 2H), 4.50-4.40 (d, 2H), 2.85(s, 3H); MS (EI) for C₂₁H₁₉N₅O₄: 406 (MH⁺).

3-amino-N-methyl-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl]phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.20 (t, 1H), 8.88 (s, 1H), 8.86-8.78 (d,1H), 8.54 (s, 1H), 8.42-8.36 (d, 1H), 7.90-7.84 (d, 1H), 7.64-7.58 (t,1H), 7.52-7.46 (d, 2H), 7.38-7.32 (d, 2H), 4.56-4.50 (d, 2H), 2.90-2.80(t, 3H); MS (EI) for C₂₁H₁₈N₅O₃F₃: 446 (MH⁺).

3-amino-6-{3-[({[4-fluoro-3-(trifluoromethyl)phenyl]methyl}aminocarbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.24-9.18 (t, 1H), 8.90 (s, 1H), 8.86-8.80(d, 1H), 8.52 (s, 1H), 8.42-8.37 (d, 1H), 7.90-7.84 (d, 1H), 7.80-7.72(m, 2H), 7.62-7.58 (q, 1H), 7.54-7.48 (t, 1H), 4.60-4.55 (d, 2H),3.78-3.68 (d, 3H); MS (EI) for C₂₁H₁₇N₅O₂F₄ 448 (MH⁺).

3-amino-6-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.28-9.22 (t, 1H), 8.90 (s, 1H), 8.88-8.82(d, 1H), 8.52 (s, 1H), 8.44-8.36 (d, 1H), 7.90-7.82 (m, 2H), 7.74-7.66(q, 2H), 7.60-7.54 (t, 1H); MS (EI) for C₂₁H₁₇N₅O₂F₃Cl: 464 (MH⁺).

Example 5

3-amino-6-[3-(hydroxy-benzylcarbamoyl)-phenyl]-pyrazine-2-carboxylicacid methylamide isomers

Scheme 5 shows how3-amino-6-[3-(hydroxy-benzylcarbamoyl)-phenyl]-pyrazine-2-carboxylicacid methylamide isomers were made. Methoxy benzylamines weredemethylated via acidic hydrolysis to give the corresponding aminehydrobromide salts, (xxviii). These were used to make compounds (xxix)via amide forming reaction, for example using standard amide couplingreagents as depicted in Scheme 5. Exemplary details are set forth below.

3-amino-6-(3-{[(2-hydroxybenzyl)amino]carbonyl}phenyl)-N-methyl-2-pyrazine-carboxamidetrifluoroacetate: A solution of 3.0 mL (0.023 mol){[2-(methoxy)phenyl]methyl}amine was refluxed in 50 mL 33% HBr inglacial acetic acid until the full deprotection of the startingmaterial. The solvent was evaporated to obtain 4.7 g2-(aminomethyl)phenol hydrobromide: MS (EI) for C₇H₉NO: 124.1 (MH+).

To a solution of 54 mg (0.20 mmol)3-{5-amino-6-[(methylamino)carbonyl]-2-pyrazinyl}benzoic acid in DMF (5mL), 165 mg (1.20 mmol) 1-hydroxybenztriazol (HOBt), 380 mg (1.00 mmol)O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU) and 0.22 mL (2.00 mmol) 4-methylmorpholine was added and thereaction mixture was stirred for 30 minutes at room temperature,followed by the addition of 41 mg (0.20 mmol) 2-(aminomethyl)phenolhydrobromide The reaction mixture was stirred at room temperature for 18h. The reaction was diluted with ethyl acetate washed sequentially withwater, 1.0 M aqueous hydrochloric acid, water and saturated aqueoussodium chloride. The organic layer was dried over sodium sulfate,filtered, and concentrated on a rotary evaporator under reducedpressure. The crude product was purified by HPLC (reverse-phase,CH₃CN/H₂O with 0.1% TFA). Upon removal of solvent, the product was takenup in methanol. Removal of solvent in vacuo provided 54 mg (55% yield)of title product: ¹H NMR (400 M, d₆-DMSO): 9.02 (t, 1H), 8.84 (s, 1H),8.78 (q, 1H), 8.50 (s, 1H), 8.36 (d, 1H), 7.78 (d, 1H), 7.54 (t, 1H),7.22 (m, 2H), 6.94 (m, 2H), 4.86 (bs, 1H), 4.40 (d, 2H), 2.80 (d, 3H).MS (EI) for C₂₀H₁₉N₅O₃: 378.5 (MH+).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-(3-{[(3-hydroxybenzyl)amino]carbonyl}phenyl)-N-methyl-2-pyrazine-carboxamidetrifluoroacetate: ¹H NMR (400 MHz, d₆-DMSO): 9.02 (t, 1H), 8.86 (s, 1H),8.80 (q, 1H), 8.54 (s, 1H), 8.36 (d, 1H), 7.86 (d, 1H), 7.58 (t, 1H),7.15 (m, 2H), 6.94 (s, 1H), 6.76 (m, 1H), 4.94 (bs, 1H), 4.43 (d, 2H),2.82 (d, 3H). MS (EI) for C₂₀H₁₉N₅O₃: 378.4 (MH+).

3-amino-6-(3-{[(4-hydroxybenzyl)amino]carbonyl}phenyl)-N-methyl-2-pyrazine-carboxamidetrifluoroacetate: ¹H NMR (400 MHz, d₆-DMSO) 9.04 (t, 1H), 8.88 (s, 1H),8.84 (q, 1H), 8.54 (s, 1H), 8.40 (d, 1H), 7.86 (d, 1H), 7.60 (t, 1H),7.18 (d, 2H), 6.86 (d, 2H), 5.02 (bs, 1H), 4.43 (d, 2H), 2.82 (d, 3H).MS (EI) for C₂₀H₁₉N₅O₃: 378.4 (MH+).

Example 6

3-amino-N-methyl-6-{3-[({2-[2-(4-morpholinyl)ethoxy]benzyl}amino)carbonyl]phenyl}-2-pyrazinecarboxamide

Scheme 6 shows how3-Amino-6-{3-[3-(morpholin-4-yl-ethoxy)-benzylcarbamoyl]-phe-nyl}-pyrazine-2-carboxylicacid methylamide isomers were made. Benzylamine hydrobromide salts(xxviii) (refer to Scheme 5) were converted to the correspondingBoc-protected derivatives (xxx). These were used to make compounds(xxxi), for example via Mitsinobu reaction. Intermediates (xxxi) wereused to make compounds (xxxii) via amide forming reaction, for exampleusing standard amide coupling reagents as depicted in Scheme 6.Exemplary details are set forth below.

3-amino-N-methyl-6-{3-[({2-[2-(4-morpholinyl)ethoxy]benzyl}amino)carbonyl]phe-nyl}-2-pyrazinecarboxamide:To an ice-cold solution of 4.0 g (0.02 mol) 2-(aminomethyl)phenolhydrobromide was added 8.40 g (0.10 mol) sodium bicarbonate in 10%aqueous THF (150 mL) followed by 22 mL (0.022 mol) di-tert-butyldicarbonate (1M in THF) and the reaction mixture was stirred at roomtemperature for 18 h. It was diluted with ethyl acetate and washedsequentially with water, 1.0 M aqueous hydrochloric acid, water andsaturated aqueous sodium chloride. The organic layer was dried oversodium sulfate, filtered, and concentrated on a rotary evaporator underreduced pressure. The solvent was evaporated to obtain 4.2 g1,1-dimethylethyl-[(2-hydroxyphenyl)-methyl]carbamate. MS (EI) forC₁₂H₁₇NO₃: 123.4 (M-Boc), 167.4 (M-tBu).

To an ice-cold solution of 3.30 g (0.015 mol)1,1-dimethylethyl-[(2-hydroxyphenyl)-methyl]carbamate, 2.20 mL (0.018mol) 2-morpholin-4-ylethanol and 4.80 g (0.019 mol) triphenylphosphinein a mixture of tetrahydrofuran-dichloromethane (2:1) (150 mL), 3.74 mL(0.019 mol) diisopropyl azodicarboxylate was added dropwise. Thereaction mixture was stirred for 18 h. It was diluted with ethyl acetateand washed sequentially with water then saturated aqueous sodiumchloride. The organic layer was dried over sodium sulfate, filtered andconcentrated on a rotary evaporator under reduced pressure. Theresulting crude material was purified by silca gel column chromatographyto yield 3.6 g1,1-dimethylethyl-({2-[(2-morpholin-4-ylethyl)oxy]pheny}methyl)carbamate,71%. MS (EI) for C₁₈H₂₈N₂O₄: 337.4 (MH+), 236.4 (M-Boc).

Weight, 0.35g (1.0 mmol), of1,1-dimethylethyl-({2-[(2-morpholin-4-ylethyl)oxy]pheny}methyl)carbamate was taken into dichloromethane (2 mL) and treated with 2.0 mLtrifluoroacetic acid for 30 minutes at room temperature. The solvent wasevaporated and the resulting crude({2-[(2-morpholin-4-ylethyl)oxy]phenyl}methyl]trifluoroacetate, MS (EI)for C₁₃H₂₀N₂O₂: 337.4 (MH⁺) was coupled with 0.27 g (1.00 mmol)3-{5-amino-6-[(methylamino)carbonyl]-2-pyrazinyl}benzoic acid asdescribed above. The reaction was diluted with ethyl acetate, washedsequentially with water, and saturated aqueous sodium chloride. Theorganic layer was dried over sodium sulfate, filtered and concentratedon a rotary evaporator under reduced pressure. The crude product waspurified by HPLC (reverse-phase, CH₃CN/H₂O with 0.1% TFA) Upon removalof solvent, the product was taken up in a mixture of 10% methanol inethyl acetate (100 mL) and washed with saturated aqueous sodiumbicarbonate (2×30 mL) then brine. The organic layer was dried overanhydrous sodium sulfate, filtered and concentrated in vacuo to provide0.22 g title product, 44% yield. ¹H NMR (400 MHz, d₆-DMSO): 9.04 (t,1H), 8.84 (s, 1H), 8.80 (q, 1H), 8.54 (s, 1H), 8.38 (d, 1H), 7.82 (d,1H), 7.60 (t, 1H), 7.18 (m, 2H), 6.96 (m, 2H), 4.44 (d, 2H), 4.04 (m,2H), 3.85 (t, 4H), 2.84 (d, 3H) 2.78 (m, 2H), 2.37 (t, 4H). MS (EI) forC₂₆H₃₀N₆O₄: 491.5 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-N-methyl-6-{3-[({3-[2-(4-morpholinyl)ethoxy]benzyl}amino)carbonyl]phe-nyl}-2-pyrazinecarboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.03 (t, 1H), 8.86 (s, 1H), 8.84 (q, 1H),8.54 (s, 1H), 8.38 (d, 1H), 7.84 (d, 1H), 7.58 (t, 1H), 7.14 (m, 2H),6.92 (s, 1H), 6.74 (m, 1H), 4.40 (d, 2H), 4.02 (m, 2H), 3.84 (t, 4H),2.80 (d, 3H) 2.76 (m, 2H), 2.34 (t, 4H). MS (EI) for C₂₆H₃₀N₆O₄: 491.5(MH+).

3-amino-N-methyl-6-{3-[({4-[2-(4-morpholinyl)ethoxy]benzyl}amino)carbonyl]phenyl}-2-pyrazinecarboxamide: ¹H NMR (400 MHz, d₆-DMSO): 9.02 (t, 1H),8.88 (s, 1H), 8.84 (q, 1H), 8.52 (s, 1H), 8.37 (d, 1H), 7.82 (d, 1H),7.58 (t, 1H), 7.16 (d, 2H), 6.84 (d, 2H), 4.42 (d, 2H), 4.06 (m, 2H),3.82 (t, 4H), 2.82 (d, 3H) 2.78 (m, 2H), 2.36 (t, 4H). MS (EI) forC₂₆H₃₀N₆O₄: 491.5 (MH+).

3-amino-6-(3-{[(2-methoxybenzyl)amino]carbonyl}phenyl)-N-methyl-2-pyrazine-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.03 (t, 1H), 8.86 (s, 1H), 8.84 (q, 1H),8.52 (s, 1H), 8.40 (d, 1H), 7.82 (d, 1H), 7.56 (t, 1H), 7.20 (m, 2H),6.96 (m, 2H), 4.44 (d, 2H), 3.64 (s, 3H), 2.84 (d, 3H). MS (EI) forC₂₁H₂₁N₄O₃: 392.4 (MH+).

3-amino-N-methyl-6-[3-({[4-(4-methyl-1-piperazinyl)benzyl]amino}carbonyl)phe-nyl]-2-pyrazinecarboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.04 (t, 1H), 8.86 (s, 1H), 8.82 (dd, 1H),8.52 (s, 1H), 8.38 (d, 1H), 7.84 (d, 1H), 7.58 (t, 1H), 7.20 (d, 2H),6.84 (d, 2H), 4.43 (d, 2H), 3.08 (t, 4H), 2.82 (d, 3H), 2.42 (t, 2.20(s, 3H) MS (EI) for C₂₅H₂₉N₇O₂: 460.2 (MH+).

Example 7

3-amino-6-[3-({[(4-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide

A solution of 3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoicacid (0.10 g, 0.37 mmol), HOBt (0.055 g, 0.41 mmol) and HBTU (0.15 g,0.41 mmol) in DMF (1.2 mL) was stirred at r.t. for 10 min. A solution of[4-(aminomethyl)phenyl]amine (0.050 mL, 0.44 mmol) in DMF (1.0 mL) wasadded and the resulting solution was stirred for 12 h at r.t. Thesolution was concentrated in vacuo and the crude mixture was partitionedbetween EtOAc (100 mL) and brine (50 mL). The organic layer was washedwith brine (2×50 mL) and the organic layer was dried (Na₂SO₄), filteredand concentrated in vacuo. The residue was purified via columnchromatography (SiO₂, 5% MeOH/CH₂Cl₂) and trituration of the productgave 0.035 g (39% yield) of product: ¹H NMR (400 MHz, d₆-DMSO): 8.95 (t,1H), 8.91 (s, 1H), 8.84 (m, 1H), 8.50 (m, 1H), 8.37 (dt, 1H), 7.87 (dt,1H), 7.56 (t, 1H), 7.01 (d, 2H), 6.52 (m, 2H), 4.97 (s, 2H), 4.35 (d,2H), 2.85 (d, 3H); MS (EI) for C₂₀H₂₀N₆O₂: 377 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-[3-({[(2-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide.¹H NMR (400 MHz, d₆-DMSO): 9.02 (t, 1H), 8.90 (s, 1H), 8.84 (m, 1H),8.51 (m, 1H), 8.38 (dt, 1), 7.88 (dt, 1H); 7.58 (t; 1H); 7.07 (m, 1H),6.97 (dt, 1H), 6.63 (dd, 1H), 6.52 (dt, 1H), 5.19 (s, 2H), 4.38 (d, 2H),2.85 (d, 3H); MS (EI) for C₂₀H₂₀N₆O₂: 377 (MH⁺).

3-amino-6-[3-({[(3-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide.¹H NMR (400 MHz, d₆-DMSO): 9.03 (t, 1H), 8.91 (s, 1H), 8.84 (m, 1H),8.53 (m, 1H), 8.39 (dt, 1H), 7.89 (dt, 1H), 7.58 (t, 1H), 6.96 (t, 1H),6.54 (m, 1H), 6.48 (d, 1H), 6.43 (m, 1H), 5.05 (s, 2H), 4.40 (d, 2H),2.85 (d, 3H); MS (EI) for C₂₀H₂₀N₆O₂: 377 (MH⁺).

3-amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide.¹H NMR (400 MHz, d₆-DMSO): 9.01 (t, 1H), 8.91 (s, 1H), 8.85 (m, 1H),8.51 (s, 1H), 8.37 (d, 1H), 7.87 (d, 1H), 7.56 (t, 1H), 7.18 (d, 2H),6.70 (d, 2H), 4.41 (d, 2H), 2.85 (m, 9H); MS (EI) for C₂₂H₂₄N₆O₂: 405(MH⁺).

3-amino-6-[3-({[(3-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide.¹H NMR (400 MHz, d₆-DMSO): 9.19 (t, 1H), 8.91 (s, 1H), 8.85 (m, 1H),8.53 (m, 1H), 8.39 (dt, 1H), 7.89 (dt, 1H), 7.59 (t, 1H), 7.56 (s, 1H),7.47 (m, 1H), 7.37 (d, 1H), 7.32 (t, 1H), 4.53 (d, 2H), 2.86 (d, 3H); MS(EI) for C₂₀H₁₈N₅O₂Br: 440 (M⁺).

3-amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide.¹H NMR (400 MHz, d₆-DMSO): 9.19 (t, 1H), 8.91 (m, 1H), 8.85 (m, 1H),8.53 (m, 1H), 8.39 (m, 1H), 7.88 (m, 1H), 7.58 (t, 1H), 7.54 (d, 2H),7.34 (d, 2H), 4.50 (d, 2H), 2.86 (d, 3H).

3-amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide.¹H NMR (400 MHz, d₆-DMSO): 9.20 (m, 1H), 8.93 (m, 1H), 8.86 (m, 1H),8.58 (m, 1H), 8.41 (d, 1H), 7.91 (m, 1H), 7.64 (d, 1H), 7.60 (t, 1H),7.39 (m, 2H), 7.24 (m, 1H), 4.57 (d, 2H), 2.85 (d, 3H); MS (EI) forC₂₀H₁₈N₅O₂Br: 442 (M⁺+2).

Example 8

3-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide

Scheme 7 shows how3-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamidewas made. (4-Morpholin-4-yl-phenyl)-methanol (xxxiii) was converted tothe corresponding amine (xxxiv). Amine (xxxiv) was used to make compound(xxxv) via amide forming reaction, for example using standard amidecoupling reagents as depicted in Scheme 7. Exemplary details and furtheranalogous examples are set forth below.

A solution of (3-morpholin-4-ylphenyl)methanol (0.10 g, 0.52 mmol), inTHF (1.0 mL) was cooled to 0° C. and DPPA (0.13 mL, 0.62 mmol) wasadded, followed by DBU (0.093 mL, 0.62 mmol). The solution was allowedto warm to r.t. and stirred for 12 h. The solution was poured into EtOAc(100 mL) and this was washed with H₂O (50 mL) and 5% HCl(aq) (50 mL).The organic layer was dried (Na₂SO₄), filtered and concentrated in vacuoto give 0.16 g (>100% yield) of 4-[3-(azidomethyl)phenyl]morpholine,(TLC: UV active spot, R_(f) of 0.7 in 1:1 hexanes/EtOAc), which was usedwithout further purification.

To a solution of 10% Pd/Carbon (0.030 g, 0.029 mmol) in 10% aqueous MeOH(4.2 mL) was added 4-[3-(azidomethyl)phenyl]morpholine (0.16 g, 0.71mmol) in MeOH (4.2 mL), and the solution was stirred vigorously under aH₂(g) balloon for 3 h. The solution was filtered through celite/frittedglass funnel and concentrated in vacuo. The crude residue was purifiedvia HPLC (reverse-phase, CH₃CN/H₂O with 0.1% TFA) and fractionscontaining the desired product were concentrated in vacuo, to provide0.064 g (29% yield) of [(3-morpholin-4-ylphenyl)methyl]aminetrifluoroacetate.

A solution of 3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoicacid (0.081 g, 0.30 mmol), HOBt (0.048 g, 0.36 mmol) and HBTU (0.17 g,0.45 mmol) in DMF (1.0 mL) was stirred at r.t. for 10 min. A solution of[(3-morpholin-4-ylphenyl)methyl]amine trifluoroacetate (0.13 g, 0.30mmol) in DMF (1.0 mL) was added and the resulting solution was stirredfor 12 h at r.t. The solution was concentrated in vacuo and the crudemixture was purified via HPLC (reverse-phase, CH₃CN/H₂O with 0.1% TFA).Upon removal of CH₃CN/H₂O, the product was taken up in EtOAc (100 mL)and washed with 1M NaOH(aq) (50 mL). The organic layer was dried(Na₂SO₄), filtered and concentrated in vacuo. Trituration and collectionof a solid by vacuum filtration provided 11.6 mg (and treated withBio-Rad AG 1-X8 resin (hydroxide form) until pH 8. The product wasfiltered and concentrated in vacuo, to provide 14.1 mg (9% yield) of3-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide: ¹H NMR (400 MHz, d₆-DMSO): 9.15 (t, 1H),8.91 (s, 1H), 8.87 (m, 1H), 8.55 (s, 1H), 8.37 (d, 1H), 7.88 (d, 1H),7.57 (t, 1H), 7.19 (t, 1H), 6.95 (s, 1H), 6.82 (m, 2H), 4.48 (d, 2H),3.72 (t, 4H), 3.08 (t, 2H), 2.85 (d, 3H); MS (EI) for C₂₄H₂₆N₆O₃: 447(MH⁺).

Using the analogous synthetic techniques beginning from commerciallyavailable [(2-morpholin-4-ylphenyl)methyl]amine and[(4-morpholin-4-ylphenyl)methyl]amine, the following compounds of theinvention were prepared:

3-amino-N-methyl-6-[3-({[(2-morpholin-4-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide: ¹H NMR (400 MHz, d₆-DMSO): 9.06 (t, 1H),8.92 (s, 1H), 8.85 (m, 1H), 8.56 (s, 1H), 8.39 (d, 1H), 7.91 (d, 1H),7.58 (t, 1H), 7.31 (d, 1H), 7.25 (t, 1H), 7.15 (d, 1H), 7.09 (t, 1H),4.65 (d, 2H), 3.77 (m, 4H), 2.89 (m, 2H), 2.85 (d, 3H); MS (EI) forC₂₄H₂₆N₆O₃: 447 (MH⁺).

3-amino-N-methyl-6-[3-({[(4-morpholin-4-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.16 (t, 1H), 8.91 (s, 1H), 8.88 (m, 1H),8.56 (s, 1H), 8.37 (dt, 1H), 7.88 dt, 1H), 7.56 (t, 1H), 7.23 (d, 2H),6.91 (d, 2H), 4.43 (d, 2H), 3.72 (m, 4H), 3.06 (m, 2H), 2.85 (d, 3H); MS(EI) for C₂₄H₂₆N₆O₃: 447 (MH⁺).

Methyl 3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate: Amixture of 3-amino-6-bromopyrazine-2-cyclopropylcarboxamide (5.0 g, 19.4mmole),[1,1′bis-(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethanecomplex (0.88 g, 1.9 mmol), 3-carbomethoxyphenylboronic acid (4.2 g,23.3 mmol) in DMF (30 mL) was de-gassed with nitrogen. Triethylamine(5.4 mL, 38.9 mmol) was then added and the resulting mixture was heatedat 85° for 2.5 hours. The reaction mixture was cooled to roomtemperature, diluted with ethyl acetate (200 mL), filtered over silicagel, washed with saturated sodium bicarbonate solution (150 mL), driedover sodium sulfate, filtered, and concentrated. The oily residue waspurified by flash chromatography (silica gel, eluted with ethylacetate-hexanes gradient from 15% to 80% yield) to give methyl3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate (a tancolor solid, 4.5 g, 74% yield): ¹H NMR (400 MHz, DMSO-d₆): 8.67 (s, 1H),8.50-8.49 (t, 1H), 8.07-8.03 (m, 2H), 7.57-7.54 (t, 1M), 3.98 (s, 3H),2.91-2.88 (m, 1H), 0.94-0.85 (m, 2H), 0.72-0.62 (m, 2H); MS (EI) forC₁₆H₁₆N₄O₃: 428 (MH⁺).

Methyl 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate: Amixture of 3-amino-6-bromopyrazine-2-ethylcarboxamide (5.0 g, 20.4mmol),[1,1′bis-(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethanecomplex (0.93 g, 2.04 mmol), 3-carbomethoxyphenylboronic acid (4.4 g,24.4 mmol) in DMF (30 mL) was de-gassed with nitrogen. Triethylamine(5.7 mL, 40.1 mmol) was then added and the resulting mixture was heatedat 85° for 2.5 hours. The reaction mixture was cooled to roomtemperature, diluted with ethyl acetate (200 mL), filtered over silicagel, washed with saturated sodium bicarbonate solution (150 mL), driedover sodium sulfate, filtered, and concentrated. The oily residue waspurified by flash chromatography (silica gel, eluted with ethylacetate-hexanes gradient from 15% to 80% yield) to give methyl3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate (4.3 g, 70%yield): ¹H NMR (400 MHz, CDCl₃): 8.66 (s, 1H), 8.53-8.52 (t, 1H),8.08-8.06 (m, 2H), 8.00 (b, 1H), 3.5 (t, 1H), 3.97 (s, 3H), 2.91-2.88(m, 1H), 0.94-0.85 (m, 2H), 0.72-0.62 (m, 2H); MS (EI) for C₁₅H₁₆N₄O₃:301 (MH⁺).

3-amino-N-ethyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:Methyl 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate (480 mg,1.6 mmol) was suspended in a 20 mL of 1:1 MeOH-5% aqueous sodiumhydroxide and heated at 90-95° C. for 4 hours. The homogeneous reactionmixture was cooled to room temperature, concentrated to half the initialvolume, cooled in an ice-bath, and acidified to pH of 4 withconcentrated HCl. A white solid precipitated and was collected, washedwith water and dried in vacuo to give3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoic acid (445 mg,97% yield). The pyrazine acid (40 mg, 0.14 mmol) was dissolved in DMF (1mL), and then 1-hydroxybenzotriazole (30 mg, 0.22 mmol),1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (30 mg,0.16 mmol), and 4-methylmorpholine (30 mg, 0.28 mol) were addedsequentially. After one hour benzylamine (30 mg, 0.27 mmol) was added tothe reaction mixture and stirring was continued at room temperature for18 hours. The mixture was then diluted with ethyl acetate (10 mL),washed with water, saturated sodium bicarbonate solution then brine anddried over sodium sulfate, filtered, and concentrated. The oily residuewas purified by flash chromatography (silica gel, eluted with ethylacetate-hexanes gradient from 15% to 80% yield) to give3-amino-N-ethyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide(a tan color solid, 22 mg, 42% yield): ¹H NMR (400 MHz, DMSO-d₆): 9.14(s, 1H), 8.88 (s, 1H), 8.87-8.85 (b, 1H), 8.51 (s, 1H), 8.37-8.34 (d,1H), 7.87-7.85 (d, 1H), 7.63-7.59 (b, 1H), 7.58-7.54 (t, 1), 7.34-7.23(m, 4H), 4.53-4.52 (d, 2H), 3.38-3.29 (m, 2H), 1.171.14 (t, 3H); MS (EI)for C₂₁H₂₁N₅O₂: 376 (MH⁺).

3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-ethylpyrazine-2-carboxamide:Methyl 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate (480 mg,1.6 mmol) was suspended in a 20 mL of 1:1 MeOH-5% aqueous sodiumhydroxide and heated at 90-95° C. for 4 hours. The homogeneous reactionmixture was cooled to room temperature, concentrated to half the initialvolume, cooled in an ice-bath, and acidified to pH 4 with concentratedHCl. A white solid precipitated and was collected by filtration, washedwith water and dried in vacuo to give3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoic acid (445 mg,97% yield). The acid (40 mg, 0.14 mol) was dissolved in DMF (1 mL) and1-hydroxybenzotriazole (30 mg, 0.22 mmol),1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (30 mg,0.16 mmol), and 4-methylmorpholine (30 mg, 0.28 mol) were addedsequentially. After one hour, 2-chloro-6-fluorobenzylamine (30 mg, 0.19mmol) was added to the reaction mixture and stirring was continued atroom temperature for 18 hours. It was then diluted with ethyl acetate(10 mL), washed with water, saturated sodium bicarbonate solution, andbrine, dried over sodium sulfate, filtered, and concentrated. The oilyresidue was purified by flash chromatography (silica gel, eluted withethyl acetate-hexanes gradient from 15% to 80% yield) to give3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-ethylpyrazine-2-carboxamide(a tan color solid, 31 mg, 51% yield): ¹H NMR (400 MHz, DMSO-d₆): 8.86(s, 1H), 8.85-8.83 (b, 1H), 8.45 (s, 1H), 8.33-8.31 (d, 1H), 7.83-7.81(d, 1H), 7.53-7.51 (t, 1H), 7.39-7.34 (m, 2H), 7.26-7.21 (t, 1H),4.63-4.61 (d, 2H), 3.38-3.29 (m, 2H), 1.15-1.11 (t, 3H); MS (EI) forC₂₁H₁₉ClFN₅O₂: 428 (MH⁺).

3-amino-N-cyclopropyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:Methyl 3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate(480 mg, 1.5 mmol) was suspended in a 20 mL of 1:1 MeOH-5% aqueoussodium hydroxide and heated at 90-95° C. for 4 hours. The homogeneousreaction mixture was cooled to room temperature, concentrated to halfthe initial volume, cooled in an ice-bath, and acidified to pH 4 withconcentrated HCl. A white solid precipitated and was collected byfiltration, washed with water and dried in vacuo to give theintermediate3-{5-amino-6[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoic acid. Theacid (40 mg, 0.13 mmol) was dissolved in DMF (1 mL) and1-hydroxybenzotriazole (30 mg, 0.22 mmol),1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (30 mg,0.16 mmol), and 4-methylmorpholine (30 mg, 0.28 mol) were addedsequentially. After one hour benzylamine (30 mg, 0.27 mmol) was added tothe reaction mixture and stirring was continued at room temperature for18 hours. It was then diluted with ethyl acetate (10 mL), washed withwater, saturated sodium bicarbonate solution, and brine, dried oversodium sulfate, filtered, and concentrated. The oily residue waspurified by flash chromatography (silica gel, eluted with ethylacetate-hexanes gradient from 15% to 80% yield) to give3-amino-N-cyclopropyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide (a tan color solid, 23 mg, 44% yield): ¹H NMR(400 MHz, DMSO-d₆): 9.14 (t, 1H), 8.88 (s, 1H), 8.69-8.68 (d, 1H), 8.51(s, 1H), 8.34-8.32 (d, 1H), 7.87-7.85 (d, 1H), 7.63-7.59 (b, 1H),7.57-7.53 (t, 1H), 7.34-7.23 (m, 4H), 4.53-4.52 (d, 2H), 2.84-2.82 (m,1H), 0.75-0.70 (m, 4H); MS (EI) for C₂₂H₂₁N₅O₂388 (MH⁺).

3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-cyclopropylpyrazine-2-carboxamide:Methyl 3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate(480 mg, 1.5 mmol) was suspended in a 20 mL of 1:1 MeOH-5% aqueoussodium hydroxide and heated at 90-95° C. for 4 hours. The homogeneousreaction mixture was cooled to room temperature, concentrated to halfthe initial volume, cooled in an ice-bath, and acidified to pH 4 withconcentrated HCl. A white solid precipitated and was collected byfiltration, washed with water and dried in vacuo to give theintermediate3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoic acid. Theacid (40 mg, 0.13 mmol) was dissolved in DMF (1 mL) and1-hydroxybenzotriazole (30 mg, 0.22 mmol),1-[(3-dimethylamino)propyl]pyrazin-2-ethylcarbodiimide hydrochloride (30mg, 0.16 mmol), and 4-methylmorpholine (30 mg, 0.28 mol) were addedsequentially. After one hour 2-chloro-6-fluorobenzylamine (30 mg, 0.19mmol) was added to the reaction mixture and stirring was continued atroom temperature for 18 hours. It was then diluted with ethyl acetate(10 mL), washed with water, saturated sodium bicarbonate solution, andbrine, dried over sodium sulfate, filtered, and concentrated. The oilyresidue was purified by flash chromatography (silica gel, eluted withethyl acetate-hexanes gradient from 15% to 80% yield) to give3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-cyclopropyl-pyrazine-2-carboxamide(a tan color solid, 23 mg, 56% yield): ¹H NMR (400 MHz, DMSO-d₆):8.87-8.86 (t, 1H), 8.85-8.83 (b, 1H), 8.65-8.64 (d, 1H), 8.45 (s, 1H),7.83-7.81 (d, 1H), 7.53-7.51 (t, 1H), 7.41-7.39 (m, 2H), 7.26-7.21 (t,1H), 4.63-4.61 (d, 2H), 2.85-2.81 (m, 1H), 0.73-0.64 (m, 4H); MS (EI)for C₂₂H₁₉ClFN₅O₂: 440 (MH⁺).

3-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2-carboxamide:3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid (40 mg,0.15 mmol) was dissolved in DMF (1 mL) and 1-hydroxybenzotriazole (30mg, 0.22 mmol), 1-[(3-dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride (30 mg, 0.16 mmol), and 4-methylmorpholine (30 mg, 0.28mol) were added sequentially. After one hour phenylhydrazine (30 mg,0.27 mmol) was added to the reaction mixture and stirring was continuedat room temperature for 18 hours. It was then diluted with ethyl acetate(10 mL), washed with water, saturated sodium bicarbonate solution, andbrine, dried over sodium sulfate, filtered, and concentrated. The oilyresidue was purified by flash chromatography (silica gel, eluted withethyl acetate-hexanes gradient from 15% to 80% yield) to give3-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2-carboxamide(a tan color solid, 30 mg, 56% yield): ¹H NMR (400 MHz, DMSO-d₆): 10.42(b, 1H), 8.92 (s, 1H), 8.84-8.82 (b, 1H), 8.57-8.57 (s,1H0, 8.41-8.39(d, 1H), 7.94-7.89(m, 1H), 7.89-7.86 (d, 1H), 7.61-7.57 (t, 1H),7.17-7.13 (t, 1H), 6.83-6.80 (d, 1H), 6.73-6.69(m, 1H), 2.85 (s, 3H); MS(EI) for C₁₉H₁₈N₆O₂: 440 (MH⁺).

Example 9

4-{5-amino-6-[(methylamino)carbonyl-]pyrazin-2-yl}benzoic acid

Phenylmethyl 4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoate:To a stirred mixture of 3-amino-6-bromo-N-methyl-2-pyrazinecarboxamide(0.577 g, 2.5 mmol), 4-benzyloxycarbonylphenylboronic acid (0.768 g, 3.0mmol), triethylamine (1.01 g, 10 mmol) in 10 mL of DMF was added[1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complexwith dichloromethane (1:1), (20.4 mg, 0.025 mmol). The stirred mixturewas warmed to 80-90° C. for 12 h and then concentrated on a rotaryevaporator under reduced pressure. The residue was dissolved in 50 mL ofEtOAc, washed with brine (30 mL). The organic layer was filtered throughcelite, and then dried over anhydrous sodium sulfate. Filtration,concentration and column chromatography on silica EtOAc) gave a solid(450 mg, 59.7% yield). ¹H NMR (400 MHz; DMSO-d₆): 8.91 (s, 1H); 8.84 (brs, 1H); 8.33 (d, 2H); 8.02 (d, 2H); 7.30-7.48 (m, 5H); 5.38 (s, 2H);2.86 (s, 3M); MS (EI) for C₂₀H₁₅N₄O₃: 363 (MH⁺).

4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid: A flaskwas charged with phenylmethyl 4-[5-amino-6-(methylamino)carbonyl)pyrazin-2-yl}benzoate (0.37 g, 1.01 mmol) and 10 mL of a solution of 1 Naqueous LiOH. The mixture was refluxed for 15 min. and then allowed tocool to room temperature. The mixture was extracted with ethyl acetate(10 mL). The pH of the aqueous phase was adjusted to pH of 2-3 with 10%aqueous HCl. The resulting solid product was collected by filtration,washed with water, and dried, to afford4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid (0.150 mg,54.2% yield): ¹H NMR (400 MHz; DMSO-d₆): 8.93 (s, 1H); 8.80 (br s, 1H);8.30 (d, 2H); 8.41 (d, 1H); 8.0 (d, 2H); 2.86 (d, 3H); MS (EI) forC₁₃H₁₂N₄O₃: 273 (MH⁺).

3-amino-N-methyl-6-(4-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 9.18 (m, 1H); 8.95 (s, 1H); 8.90 (m, 1H); 8.3(d, 2H); 8.0 (d, 2H); 7.37 (m, 5H); 4.5 (d, 2H); 2.87 (d, 3H); MS (EI)for C₂₀H₁₉N₅O₂: 362 (MH⁺).

3-amino-N-methyl-6-(4-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:MS (EI) for C₂₁H₂₁N₅O₂:376 (MH⁺)

3-amino-6-[4-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 9.18 (m, 1H); 8.97 (s, 1H); 8.90 (m, 1H); 8.3(d, 2H); 8.0 (d, 2H); 7.62 (c, 1H); 7.4 (m, 2H); 4.53 (d, 2H); 2.87 (d,3H); MS (EI) for C₂₀H₁₇N₅O₂ Cl₂: 430 (MH⁺)

3-amino-N-methyl-6-[4-({[(4-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 9.1 (m, 1H); 8.97 (s, 1H); 8.90 (m, 1H); 8.3(d, 2H); 8.0 (d, 2H); 7.2-7.1 (m, 5H); 4.53 (d, 2H); 2.87 (d, 3H); 2.25(s, 3H); MS (EI) for C₂₁H₂₁N₅O₂: 376 (MH⁺)

3-amino-6-(4-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₂H₂₁N₅O₂: 388 (MH⁺)

3-amino-N-methyl-6-[3-({[(2,4,6-trichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.86 (s, 1H); 8.8 (m, 1H); 8.68 (m, 1H); 8.42(s, 1H); 8.34 (d, 1H); 7.8 (d, 1H); 7.54 (t, 1H); 7.46 (s, 1H); 7.34 (s,1H); 4.6 (d, 2H); 2.85 (d, 3H); 2.43 (s, 3H); MS (EI) for C₂₀H₁₆N₅O₂Cl₃:465 (MH⁺)

3-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.25 (t, 1H); 8.88 (s, 1H); 8.82 (m, 1H); 8.5(m, 1H); 8.38 (d, 1H); 7.86 (d, 1H); 7.56 (t, 1H); 1H); 7.34 (d, 1H);7.28 (d, 1H); 7.2 (t, 1H); 4.5 (d, 2H); 2.85 (d, 3H); MS (EI) forC₂₁H₂₀N₅O₂Cl: 410 (MH⁺)

3-amino-6-{3-[({[2,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide: ¹H NMR (400 MHz; DMSO-D₆): 8.95 (t, 1H);8.9 (s, 1H); 8.68 (m, 1H); 8.8 (m, 1H); 8.52 (s, 1H); 8.36 (d, 1H); 7.84(d, 1H); 7.54 (t, 1H); 6.9 (d, 1H); 6.8 (m, 3H); 4.6 (d, 2H); 3.8 (s,3H); 3.62 (s, 3H); 2.85 (d, 3H); MS (EI) for C₂₁H₂₁N₅O₂: 422 (MH⁺)

3-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.1 (t, 1H); 8.85 (s, 1H); 8.8 (m, 1H); 8.52(s, 1H); 8.38 (d, 1H); 7.85 (d, 1H); 7.58 (t, 1H); 7.2 t, 1H); 4.45 (d,2H); 2.85 (d, 3H); 2.2 (s, 3H); MS (EI) for C₂₁H₂₁N₅O₂: 394 (MH⁺)

3-amino-6-[3-({[(2-chloro-6-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.85 (s, 1H); 8.8 (m, 1H); 8.53 (s, 1H); 8.38(d, 1H); 7.8 (d, 1H); 7.56 (t, 1H); 7.2 (m, 1H); 7.15 (t, 1H); 4.6 (d,2H); 2.85 (d, 3H); MS (EI) for C₂₁H₁₉N₅O₂FCl: 428 (MH⁺)

3-amino-6-[3-({[(2-chloro-3,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.9 (t, 1H); 8.85 (s, 1H); 8.8 (m, 1H); 8.49(s, 1H); 8.38 (d, 1H); 7.8 (d, 1H); 7.56 (t, 1H); 7.45 (m, 1H); 7.3 (m,1H); 4.6 (d, 2H); 2.85 (d, 3H); 2.3 (s, 3H); MS (EI) for C₂₀H₁₆N₅O₂F₂Cl:432 (MH⁺)

3-amino-6-[3-({[(2,3-difluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.1 (t, 1H); 8.9 (s, 1H); 8.8 (m, 1H); 8.53(s, 1H); 8.38 (d, 1H); 7.8 (d, 1H); 7.56 (t, 1H); 7.1 (m, 1H); 4.5 (d,2H); 2.85 (d, 3H); 2.23 (s, 3H); MS (EI) for C₂₁H₁₉N₅O₂F₂: 412 (MH⁺)

Example 10

3-Amino-N-methyl-6-{3-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide

3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide: To a solutionof 3-amino-6-bromo-pyrazine-2-carboxylic acid methylamide (1.234 g, 5.30mmol, 1.00 equiv.) in N,N-dimethylformamide (DMF, 30 mL) was added[1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complexwith dichloromethane (1:1), (Aldrich Chemical Company, 433 mg, 0.530mmol, 0.100 equiv.), 3-aminophenylboronic acid monohydrate (AldrichChemical Company, 1.149 g, 7.41 mmol, 1.40 equiv.), and triethylamine(TEA, 1.073 g, 10.6 mmol, 2.00 equiv.). Nitrogen was passed through thesolution for 3-5 min. The reaction mixture was heated at 85-90° C. for15 h with stirring. The reaction was allowed to cool to room temperatureand diluted with 400 mL of EtOAc. The mixture was washed with saturatedaqueous NaHCO₃ (2×50.0 mL), saturated aqueous NaCl (1×50.0 mL), driedover magnesium sulfate (MgSO₄), and filtered. The filtrate wasconcentrated on a rotary evaporator under reduced pressure. To the crudeproduct was added 30 mL of a 4.0M solution of anhydrous HCl in dioxane.The resulting solid was filtered and rinsed with 20% methanol in diethylether to remove impurities. The solid was dissolved in methanol andneutralized with sufficient AG 1-X8 Resin (hydroxide form) that the pHof the solution became basic. The mixture was filtered, and the filtratewas concentrated on a rotary evaporator at reduced pressure to affordthe title compound (0.695 g, 54% yield).

Example 11

3-amino-N-methyl-6-{3-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide

3-amino-N-methyl-6-{3-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide:To a solution of3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide (26 mg, 0.11mmol) in dry dichloromethane (2 mL) at 0° C. were added triethylamine(22 mg, 0.22 mmol) and methanesulfonyl chloride (20 mg, 0.17 mmol). Thereaction was slowly warmed to room temperature and stirred overnight.Reaction was treated water (10 mL) and diluted with ethyl acetate (100mL). The organic layer was washed with saturated aqueous sodiumbicarbonate (40 mL) and saturated aqueous sodium chloride (30 mL), driedover magnesium sulfate, filtered, and concentrated to afford3-amino-N-methyl-6-{3-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide(15 mg, 45% yield) as yellow solid. ¹H NMR (400 MHz, CDCl₃): 8.62 (s,1H), 7.94 (br s, 1H), 7.75 (br s, 1H), 7.68 (br d, 1H), 7.45 (t, 1H),7.30 (br d, 1H), 7.25 (br s, 1H), 3.02 (m, 6H); MS (EI) for C₁₃H₁₅N₅O₃S:322 (MH⁺).

Example 12

3-Amino-N-methyl-6-[3-({[4-(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide

To a solution of3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide (20 mg, 0.07mmol) and triethylamine (160 mg, 0.16 mmol) in tetrahydrofuran (1 mL)was added p-anisoyl chloride (20 mg, 0.12 mmol) slowly at roomtemperature. The mixture was allowed to stir overnight. The reaction wasquenched with water (10 mL) at 0° C. and diluted with ethyl acetate (200mL). The organic layer was washed with saturated aqueous sodiumbicarbonate (30 mL), saturated aqueous sodium chloride, and dried overmagnesium sulfate. The solution was filtered and concentrated at reducedpressure to afford3-amino-N-methyl-6-[3-({[4-(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide(13 mg, 48% yield) as yellow solid. ¹H NMR (400 MHz, d₆-DMSO): 10.10 (s,1H), 8.85 (s, 2H), 8.30 (s, 1H), 8.02 (d, 2H), 7.90 (m, 2H), 7.40 (m,1H), 7.02 (d, 2H), 3.80 (s, 3H), 2.82 (br s, 3H); MS (EI) forC₂₀H₁₉N₅O₃: 378 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-N-methyl-6-{3-[(phenylcarbonyl)amino]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.60 (s, 1H), 8.72 (m, 2H), 8.30 (s, 1H),8.05 (d, 2H), 7.92 (d, 1H), 7.82 (d, 1H), 7.60 (m, 3H), 7.45 (t, 1H),2.86 (d, 3H); MS (EI) for C₁₉H₁₇N₅O₂: 348 (MH⁺).

3-amino-N-methyl-6-[3-({[3-(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.50 (s, 1H), 8.72 (br s, 2H), 8.30 (s, 1H),7.92 (d, 1H), 7.85 (d, 1H), 7.50 (m, 6H), 7.20 (d, 1H), 3.90 (s, 3H),2.90 (s, 3H); MS (EI) for C₂₀H₁₉N₅O₃: 378 (MH⁺).

3-Amino-6-(3-{[(4-chlorophenyl)carbonyl]amino}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.35 (s, 1H), 8.70 (br s, 2H), 8.25 (br s,1H), 8.02 (br d, 2H), 7.92 (br d, 1H), 7.82 (br d, 1H), 7.65 (m, 2H),7.40 (t, 1H), 2.92 (s, 3H); MS (EI) for C₁₉H₁₆N₅O₂Cl: 382 (MH⁺).

3-Amino-N-methyl-6-(3-{[(4-methylphenyl)carbonyl]amino}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.20 (s, 1H), 8.70 (br s, 2H), 8.25 (s, 1H),7.82 (m, 4H), 7.40 (t, 1H), 7.15 (d, 2H), 2.80 (d, 3H), 2.40 (s, 3H); MS(EI) for C₂₀H₁₉N₅O₂: 362 (MH⁺).

3-Amino-6-{3-[(furan-2-ylcarbonyl)amino]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.20 (s, 1H), 8.70 (br s, 2H), 8.24 s, 1H),7.95 (s, 1H), 7.92 (d, 1H), 7.80 (d, 1H), 7.40 (t, 1H), 7.26 (br s, 1H),6.70 (br s, 1H), 2.80 (d, 3H); MS (EI) for C₁₇H₁₅N₅O₃: 338 (MH⁺).

3-Amino-N-methyl-6-[3-({[3-(phenyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.75 (m, 2H), 8.28 (br s, 1H), 7.92 (d, 1H),7.83 (br t, 2H), 7.64 (m, 1H), 7.58 (t, 1H), 7.45 (m, 4H), 7.26 (dd,1H), 7.20 (br t, 1H), 7.12 (br d, 2H), 2.85 (d, 3H); MS (EI) forC₂₅H₂₁N₅O₃: 440 (MH⁺).

3-Amino-6-{3-[(cyclopentylcarbonyl)amino]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.92 (s, 1H), 8.70 (m, 2H), 8.10 (br s, 1H),7.92 (d, 1H), 7.70 (d, 1H), 7.40 (t, 1H), 2.90 (m, 4H), 1.75 (br m, 8H);MS (EI) for C₁₈H₂₁N₅O₂: 340 (MH⁺).

3-Amino-6-(3-{[(4-cyanophenyl)carbonyl]amino}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.55 (br s, 1H), 8.70 (br s, 2H), 8.30 (brs, 1H), 8.15 (br d, 2H), 8.05 (br d, 2H), 7.92 (br d, 1H), 7.82 (br d,1H), 7.40 (br t, 1H), 2.82 (br s, 3H); MS (EI) for C₂₀H₁₆N₆O₂: 373(MH⁺).

Example 13

3-Amino-N-methyl-6-[3-({[(phenylmethyl)amino]carbonyl}amino)phenyl]pyrazine-2-carboxamide

3-amino-N-methyl-6-[3-({[(phenylmethyl)amino]carbonyl}amino)phenyl]pyrazine-2-carboxamide:To a solution of3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide (0.25 g, 1.03mmol) in dry tetrahydrofuran (2 mL) was added benzyl isocyanate (0.15 g,1.12 mmol). The mixture was allowed to stir overnight. The solid productwas filtered from the reaction mixture and triturated with hexane/ethylacetate (9:1). The solid was collected by filtration and dried to afford3-amino-N-methyl-6-[3-({[(phenylmethyl)amino]carbonyl}amino)phenyl]pyrazine-2-carboxamide(0.26 g, 70% yield) as light yellow solid. ¹H NMR (400 MHz, d₆-DMSO):8.80 (m, 1H), 8.64 (s, 1H), 8.02 (s, 1H), 7.68 (d, 1H), 7.58 (d, 1H),7.30 (m, 8H), 4.30 (d, 2H), 2.80 (d, 3H); MS (EI) for C₂₀H₂₀N₆O₂: 377(MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-6-[3-({[(4-fluorophenyl)amino]carbonyl}amino)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.80 (br s, 1H), 8.75 (br m, 1H), 8.70 (br s,1H), 8.65 (br s, 1H), 7.92 (br s, 1H), 7.54 (br d, 1H), 7.45 (m, 2H),7.39 (t, 1H), 7.12 (br t, 3H), 2.86 (d, 3H); MS (EI) for C₁₉H₁₇N₆O₂F:381 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(methyloxy)phenyl]amino}carbonyl)amino]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.78 (br m, 1H), 8.70 (br s, 1H), 8.59 (br d,2H), 7.92 (br s, 1H), 7.72 (br d, 1H), 7.56 (br d, 1H), 7.34 (m, 3H),6.82 (br d, 2H), 3.70 (s, 3H), 2.80 (br d, 3H); MS (EI) for C₂₀H₂₀N₆O₃:393 (MH⁺).

According to the procedure described above, from3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide and thecorresponding acids, the following compounds of the invention wereprepared:

3-amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.30 (s, 1H), 8.70 (m, 2H), 8.10 (br s, 1H),7.85 (d, 1H), 7.70 (d, 1H), 7.40 (m, 5H), 3.64 (s, 2H), 2.82 (d, 3H); MS(EI) for C₂₀H₁₈N₅O₂Cl: 396 (MH⁺).

3-amino-6-{3-[(diphenylacetyl)amino]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.52 (s, 1H), 8.70 (m, 2H), 8.20 (br t, 1H),7.85 (d, 1H), 7.72 (d, 1H), 7.32 (m, 11H), 5.20 (s, 1H), 2.82 (d, 3H);MS (EI) for C₂₆H₂₃N₅O₂: 438 (MH⁺).

3-amino-N-methyl-6-{3-[(phenylacetyl)amino]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.72 (m, 1H), 8.68 (s, 1H), 8.02 (br s, 1H),7.82 (d, 1H), 7.72 (d, 1H), 7.34 (m, 6H), 7.28 (m, 1H), 3.70 (s, 2H),2.80 (d, 3H); MS (EI) for C₂₀H₁₉N₅O₂: 362 (MH⁺).

3-amino-N-methyl-6-{3-[(3-phenylpropanoyl)amino]phenyl}pyrazine-2-carboxamide¹H NMR (400 MHz, d₆-DMSO): 8.68 (m, 2H), 8.08 (br s, 1H), 7.84 (d, 1H),7.68 (d, 1H), 7.40 (t, 1H), 7.28 (m, 5H), 7.20 (m, 1H), 2.92 (t, 2H),2.82 (d, 3H), 2.62 (t, 2H); MS (EI) for C₂₁H₂₁N₅O₂: 376 (MH⁺).

3-amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 Nz, 4-DMSO): 10.30 (s, 1H), 8.62 (m, 2H), 8.10 (s, 1H), 7.82(d, 1H), 7.62 (m, 3H), 7.40 (m, 4H), 3.92 (s, 2H), 2.82 (br s, 3H); MS(EI) for C₂₀H₁₇N₅O₂Cl₂: 430, 432 (MH⁺).

3-amino-6-(3-{[(3,4-dichlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.30 (s, 1H), 8.70 (m, 2H), 8.10 (s, 1H),7.82 (d, 1H), 7.65 (m, 5H), 7.41 (m, 2H), 3.78 (s, 2H), 2.82 (d, 3H); MS(EI) for C₂₀H₁₇N₅O₂Cl₂: 430, 432 (MH⁺).

3-amino-N-methyl-6-[3-({4-(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.40 (s, 1H), 8.80 (m, 2H), 8.10 (s, 1H),7.90 (d, 1H), 7.70 (m, 4H), 7.60 (d, 2H), 7.40 (t, 1H), 3.80 (s, 2H),2.84 (d, 3H); MS (EI) for C₂₁H₁₈N₅O₂F₃: 430 (MH⁺).

3-amino-6-{3-[(1,3-benzodioxol-5-ylacetyl)amino]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 10.20 (s, 1H), 8.70 (m, 2H), 8.10 (br s, 1H),7.85 (d, 1H), 7.70 (d, 1H), 7.40 (t, 1H), 6.58 (m, 3H), 6.01 (s, 2H),3.60 (s, 2H), 2.82 (d, 3H); MS (EI) for C₂₁H₁₉N₅O₄: 406 (MH⁺).

9H-fluoren-9-ylmethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate: ¹HNMR (400 MHz, d₆-DMSO): 9.73-9.67 (m, 1H), 8.68-8.61 (m, 2H), 8.00-7.20(m, 21H), 8.00-7.96 (m, 1H), 7.90 (d, 2H), 7.86-7.26 (m, 9H), 4.49 (d,2H), 4.32 (t, 1H), 2.84 (d, 3H); MS (EI) for C₂₇H₂₃N₅O₃: 466 (MH⁺).

phenylmethyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate: ¹H NMR (400 MHz, d₆-DMSO): 9.76 (s, 1H), 8.68-8.61 (m, 2H),8.03-7.98 (m, 1H), 8.00-7.00 (m, 2H), 7.82-7.76 (m, 1H), 7.54-7.47 (m,1H), 7.46-7.30 (m, 4H), 5.18-5.14 (m, 2H), 4.50 (d, 2H), 2.87-2.82 (m,3H); MS (EI) for C₂₀H₁₉N₅O₃: 378 (MH⁺).

(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate: ¹HNMR (400 MHz, d₆-DMSO): 9.56 (s, 1H), 8.67-8.61 (m, 2H), 8.01-7.99 (m,1H), 7.90-7.20 (m, 2H), 7.77 (d, 1H), 7.54-7.49 (m, 1H), 7.37-7.32 (m,1H), 4.56 (td, 1H), 2.85 (d, 3H), 1.72-0.68 (m, 18H); MS (EI) forC₂₃H₃₁N₅O₃: 426 (MH⁺).

1,1-dimethylethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate: ¹HNMR (400 MHz, d₆-DMSO): 9.29 (s, 1H), 8.68-8.61 (m, 2H), 7.99-7.96 (m,1H), 8.00-7.20 (br, 2H), 7.77-7.72 (m, 1H), 7.52-7.47 (m, 1H), 7.35-7.30(m, 1H), 2.83 (d, 3H), 1.47 (s, 9H); MS (EI) for C₁₇H₂₁N₅O₃: 344 (MH⁺).

Example 14

Scheme 8 depicts a general synthetic route for compounds of theinvention having substituents —W—X—Y according to formula I, wherein,for example, W is phenylene or pyridylene, X is —SO₂NH— or —C(═O)NH—wherein the phenylene or pyridylene is attached to the sulfur or thecarbon atom of X, and Y is attached to the nitrogen of X. As describedabove, W, X, and Y all are optionally substituted, but for simplicitythis is not shown here. As depicted, intermediate (xxxvi) isincorporated into a compound of the invention, (xxxviii), where Z is Nor C, and L₂ is a substructure of X. In Scheme 8, L₂ represents either—SO₂— or —C(═O)—. The sequence of transformations regarding suchintermediates may vary depending on the nature of each of W, X, and Y.For example, when L₂ is —SO₂—, the sulfonamide is typically generatedprior to the conversion of the bromo group of (xxxvi) to the boronicester group in intermediate (xxxvii). The same is true when L₂ is—C(═O)— and W is pyridylene. In cases where W is a substituted benzene,L₂ is —C(═O)—, and Y is an alkyl group, the amide bond is formed afterthe formation of (xxxviii) using synthetic steps known in the art.Conversion of (xxxvi) to (xxxvii) is carried out usingbis(pinacolato)diboron based on procedures known to those skilled in theart. The transformation of (xxxvii) to (xxxviii) is accomplished usingSuzuki coupling conditions, for example.

3-Amino-6-(4-chloro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide

Methyl 2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate:To a solution of methyl 5-bromo-2-chlorobenzoate (0.25 g, 1.01 mmol) inanhydrous dimethylsulfoxide (6 mL) were added bis(pinacolato)diboron(0.28 g, 1.10 mmol), potassium acetate (0.29 g, 3.01 mmol), and[1,1′-bis (diphenylphosphino)ferrocene]dichloropalladium(II) complexwith dichloromethane (1:1, 25 mg, 0.03 mmol). The solution was degassedby passing nitrogen gas for 3-5 min and heated at 80-85° C. for 3 h.Reaction cooled to room temperature and diluted with ethyl acetate (250mL). The organic layer was washed with saturated aqueous sodiumbicarbonate (2×40 mL) and saturated aqueous sodium chloride (50 mL),dried over magnesium sulfate, filtered, and concentrated to affordmethyl 2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate(0.12 g, 42% yield) as semi solid. 1H NMR (400 MHz, CDCl₃): 8.20 (br d,1H), 7.80 (dd, 1H), 7.43 (d, 1H), 3.92 (s, 3H), 1.25 (s, 12H); MS (EI)for C₁₄H₁₈N₄O₂BCl: 297 (MH⁺).

Methyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoate: To asolution of methyl2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0.16g, 0.55 mmol) in toluene (2 mL)) were added3-amino-6-bromo-N-methyl-2-pyrazincarboxamide (0.13 g, 0.58 mmol),tetralds(triphenylphosphin)palladium(0) (64 mg, 0.06 mmol), ethanol (2mL), and 2.0 N sodium carbonate (0.42 g, 4.00 mmol). The solution wasdegassed with nitrogen gas for 3-5 min and heated at 90-100° C. for 2 h.Reaction cooled to room temperature and diluted with ethyl acetate (200mL). The organic layer was washed water (50 mL) and saturated aqueoussodium chloride (40 mL), dried over magnesium sulfate, filtered, andconcentrated to afford crude product. Trituration with methanol (1 mL),filtration and drying gave methyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoate (96mg, 56% yield) as yellow solid. ¹H NMR (400 MHz, CDCl₃): 8.62 (br s,1H), 8.28 (d, 1H), 7.92 (dd, 2H), 7.52 (d, 1H), 4.02 (s, 3H), 3.02 (s,3H); MS (EI) for C₁₄H₁₃N₄O₂Cl: 321 (MH⁺).

5-{5-Amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoic acid:To a solution of methyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoate (96mg, 31 mmol) in methanol/tetrahydrofuran (1:1, 5.0 mL) was added 2.0 Naqueous sodium hydroxide (0.16 g, 4.00 mmol). The reaction was stirredovernight at room temperature. Reaction was neutralized with 2.0 Naqueous hydrochloric acid (4 mL) and diluted with ethyl acetate (100mL). The organic layer was washed with water (20 mL), saturated aqueoussodium chloride (30 mL), dried over magnesium sulfate, filtered, andconcentrated to afford5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoic acid(45 mg, 48% yield). ¹H NMR (400 MHz, d₆-DMSO): 13.42 (br s, 1H), 8.90(br s, 1H), 8.45 (d, 1H), 8.32 (dd, 1H), 7.85 (br s, 2H), 7.60 (d, 2H),2.82 (s, 3H); MS (EI) for C₁₃H₁₁N₄O₃Cl: 307 (MH⁺).

(d)-3-Amino-6-(4-chloro-3-{[(phenylmethyl)amino]carbony}phenyl)-N-methylpyrazine-2-carboxamide:The title compound was synthesized according to the procedure describedabove from5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoic acidand benzylamine. Yield 99%. ¹H NMR (400 MHz, d₆-DMSO): 9.10 (t, 1H),8.90 (s, 2H), 8.26 (m, 2H), 7.60 (d, 1H), 7.40 (m, 4H), 7.14 (t, 1H),4.50 (d, 2H), 2.82 (d, 3H); MS (EI) for C₂₀H₁₈N₅O₂Cl: 396, 398 ). (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared.

3-amino-6-(4-fluoro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.64 (m, 2H), 7.98 (m, 2H), 7.40 (m, 3H), 7.32(m, 1H), 7.20 (m, 2H:), 7.15 (m, 1H), 4.70 (d, 2H), 3.02 (d, 3H), MS(EI) for C₂₀H₁₈N₅O₂F: 380 (MH⁺).

3-amino-N-methyl-6-(4-(methyloxy)-3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.80 (s, 1H), 8.60 (s, 1H), 8.20 (br s, 1H),7.90 (m, 2H), 7.30 (m, 5H), 7.20 (d, 1H), 4.70 (d, 2H), 3.92 (s, 3H),3.02 (d, 3H); MS (EI) for C₂₁H₂₁N₅O₃: 392 (MH⁺).

3-amino-6-(2-fluoro-5-{[(phenylmethyl)amino]carbonyl)phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.62 (d, 1H), 8.30 (dd, 1H), 7.90 (br s, 1H),7.70 (m, 1H), 7.30 (m, 4H), 7.26 (s, 1H), 7.20 (t, 1H), 6.50 (br s, 1H),4.65 (d, 2H), 3.02 (d, 3H); MS (EI) for C₂₀H₁₈N₅O₂F: 380 (MH⁺).

Example 153-Amino-N-methyl-6-(3-{[(phenylmethyl)amino]sulfonyl}phenyl)pyrazine-2-carboxamide

3-Bromo-N-(phenylmethyl)benzenesulfonamide: To a solution of3-bromosulfonyl chloride (1.31 g, 5.14 mmol) in dry tetrahydrofuran (10mmol) at 0° C. were added triethylamine (0.62 g, 6.17 mmol) andbenzylamine (0.50 g, 4.57 mmol). The reaction was slowly warmed to roomtemperature and stirred overnight. Reaction was treated with 2.0 Naqueous hydrochloric acid (10 mL) and diluted with ethyl acetate (300mmol). The organic layer was washed with water (30 mL), saturatedaqueous sodium bicarbonate (40 mL), saturated aqueous sodium chloride(40 mL), dried over magnesium sulfate, filtered, and concentrated toafford 3-Bromo-N-(phenylmethyl)benzenesulfonamide (1.32 g, 78% yield).¹H NMR (400 MHz, CDCl₃): 7.34 (t, 1H1), 7.85 (s, 1H), 7.80 (m, 2H), 7.50(t, 1H), 7.22 (m, 5H), 4.02 (d, 2H); MS (EI) for C₁₃H₁₂NO₂SBr: 326(MH⁺).

N-(phenylmethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide:The title compounds was synthesized according to the procedure describedabove. Yield 69%. ¹H NMR (400 MHz, CDCl₃): 8.25 (s, 1H), 7.92 (m, 2H),7.43 (t, 1H), 7.23 (m, 6H), 4.12 (d, 2H), 1.23 (s, 12H); MS (EI) forC₁₉H₂₄NO₄SB: 374 (MH⁺).

3-Amino-N-methyl-6-(3-{[(phenylmethyl)amino]sulfonyl}phenyl)pyrazine-2-carboxamidewas synthesized fromN-(phenylmethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamideand 3-amino-6-bromo-N-methyl-2-pyrazincarboxamide as yellow solid. Yield20%. ¹H NMR (400 MHz, d₆-DMSO): 8.84 (s, 1H), 8.80 (m, 1H), 8.46 (d,1H), 8.38 (br s, 1H), 8.20 (t, 1H), 7.78 (d, 1H), 7.66 (t, 1H), 7.26 (m,4H), 7.18 (m, 1H), 4.02 (d, 2H), 2.82 (d, 3H); MS (EI) for C₁₉H₁₉N₅O₃S:398 (MH⁺).

Example 163-Amino-N-methyl-6-(5-{[(phenylmethyl)amino]carbonyl}pyridin-3-yl)pyrazine-2-carboxamide

5-bromo-N-(phenylmethyl)pyridine-3-carboxamide was synthesized accordingto the procedure described above from 5-bromonicotinic acid andbenzylamine. Yield 90%. ¹H NMR (400 MHz, CDCl₃): 8.83 (d, 1H), 8.72 (d,1H), 8.25 (t, 1H), 7.30 (m, 5H), 6.58 (br s, 1H), 4.62 (d, 2H); MS (EI)for C₁₃H₁₁N₂OBr: 291 (MH⁺).

N-(phenylmethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carboxamidewas synthesized according to the procedure above from5-bromo-N-(phenylmethyl)pyridine-3-carboxamide andbis(pinacolato)diboron. Yield 49%. ¹H NMR (400 MHz, CDCl₃): 9.15 (br s,1H), 9.02 (br s, 1H), 8.35 (br s, 1H), 7.32 (m, 5H), 6.42 (br, t, 1H),4.62 (d, 2H), 1.29 (s, 12H); MS (EI) for C₁₉H₂₃N₂O₃B: 339 (MH⁺).

3-amino-N-methyl-6-(5-{[(phenylmethyl)amino]carbonyl}pyridin-3-yl)pyrazine-2-carboxamidewas synthesized according to the procedure described above fromN-(phenylmethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carboxamideand 3-amino-6-bromo-N-methyl-2-pyrazincarboxamide. Yield 38%. ¹H NMR(400 MHz, d₆-DMSO): 9.58 (d, 1H), 9.36 (t, 1H), 9.02 (m, 3H), 8.86 (t,1H), 7.34 (m, 4H), 7.24 (m, 1H), 4.50 (d, 2H), 2.83 (d, 3H); MS (EI) forC₁₉H₁₈N₆O₂: 363 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-6-[5-({[(2,6-difluorophenyl)methyl]amino}carbonyl)pyridin-3-yl]-N-methylpyrazine-2-carboxamide: ¹H NMR (400 MHz, d₆-DMSO):9.54(d, 1H), 9.12 (t, 1H), 8.92 (m, 3H), 8.79 (t, 1H), 7.42 (m, 1H),7.12 (t, 2H), 4.60 (d,2H), 2.82 (d, 3H); MS (EI) for C₁₉H₁₆N₆O₂F₂: 399(MH⁺).

3-amino-6-(5-{[(biphenyl-2-ylmethyl)amino]carbonyl}pyridin-3-yl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.52 (d, 2H), 9.15 (t, 1H), 8.92 (m, 3H),8.80 (t, 1H), 7.43 (m, 8H), 7.24 (br d, 1H), 4.50 (d, 2H), 2.82 (d, 3H),MS (EI) for C₂₅H₂₂N₆O₂: 439 ) (MH⁺).

3-amino-6-(5-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}pyridin-3-yl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.52 (br t, 2H), 9.25 (t, 1H), 6.95 (t, 1H),8.92 (m, 1H), 8.82 (m, 2H), 8.80 (m, 1H), 6.82 (br s, 2H), 4.40 (br s,2H), 4.20 (s, 4H), 2.83 (d, 3H); MS (EI) for C₂₁H₂₀N₆O₄: 421 (MH⁺)

Example 173-Amino-N-methyl-6-{3-[(2-phenylethyl)amino]phenyl}-pyrazine-2-carboxamide

3-bromo-N-(2-phenylethyl)aniline: To a solution of 3-bromoaniline (3.21g, 18.60 mmol) in dry tetrahydrofuran (45 mL) were added triethylamine(2.82 g, 27.91 mmol) and phenylacetyl chloride 93.45 g, 22.30 mmol) at0° C. The reaction warmed to room temperature and stirred for 4 h. Thereaction mixture was treated with 2.0 N aqueous hydrochloric acid (20mL) at 0° C. and diluted with ethyl acetate (300 mL). The organic layerwas washed with water (20 mL), saturated aqueous sodium bicarbonate (50mL) and saturated aqueous sodium chloride (50 mL), dried over magnesiumsulfate, filtered, and concentrated to afford crudeN-(3-bromophenyl)-2-phenylacetamide (4.84 g, 86% yield) which was usedin the next step without any further purification.

To a solution of crude N-(3-bromophenyl)-2-phenylacetamide (3.02 g, 10.4mmol) in dry tetrahydrofuran (25 mL) was added 1.0 Nborane-tetrahydrofuran complex (1:1. 26 mL, 26.12 mmol) from an additionfunnel at 0° C. The reaction was refluxed under nitrogen overnight.Reaction mixture was cooled to room temperature, treated with 2.0 Naqueous sodium hydroxide (30 mL) and then stirred for 20 min. Thereaction was then cooled again at 0° C. and neutralized with 2.0 Naqueous hydrochloric acid (60 mL) and further stirred for 30 min. Theaqueous layer was extracted with ethyl acetate (3×100 mL). The organiclayer was washed with water (20 mL), saturated aqueous sodium chloride(50 mL), dried over magnesium sulfate, filtered, and concentrated toafford 3-Bromo-N-(2-phenylethyl)aniline (2.55 g, 85% yield) as brown oilwith reasonable purity: ¹H NMR (400 MHz, CDCl₃): 7.30 (t, 2H), 7.20 (m,3H), 6.95 (t, 1H), 6.78 (br d, 1H), 6.70 (t, 1H), 6.45 (dd, 1H), 3.62(br s, 1H), 3.40 (m, 2H), 2.92 (t, 2H); MS (EI) for C₁₄H₁₂NOBr: 290MH⁺).

N-(2-phenylethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilinewas synthesized according to the procedure described above from3-bromo-N-(2-phenylethyl)aniline and bis(pinacolato)diboron. Yield 72%.¹H NMR (400 MHz, CDCl₃): 7.80 (m, 2H), 7.18 (m, 5H), 7.20 (br d, 1H),6.70 (br t, 1H), 3.40(t, 2H), 2.85 (t, 2H), 1.23 (s, 12H1); MS (EI) forC₂₀H₂₆NO₂B: 324 (MH⁺)

3-Amino-N-methyl-6-{3-[(2-phenylethyl)amino]phenyl}pyrazine-2-carboxamidewas synthesized according to the procedure described above fromN-(2-phenylethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineand 3-amino-6-bromo-N-methyl-2-pyrazincarboxamide. Yield 39%. ¹H NMR(400 MHz, CDCl₃): 8.58 (s, 1H), 8.02 (br s, 1H), 7.32 (m, 3H), 7.26 (m,3H), 7.18 (br d, 1H), 7.02 (br t, 1H), 6.64 (dd, 1H), 3.82 (br s, 1H),3.51 (t, 2H), 3.02 (d, 3H), 2.94 (t, 2H); MS (EI) for C₂₀H₂₁N₅O: 348(MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-N-methyl-6-{1-[(phenylmethyl)amino]isoquinolin-7-yl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 11.15 (m, 1H), 9.64 (s, 1H), 9.30 (m, 1H),9.15 (s, 1H), 8.84 (m, 1H), 8.03 (m, 1H), 7.58 (m, 1H), 7.50 (m, 2H),7.37 (m, 2H), 7.28 (m, 2H), 5.08 (br s, 2H), 4.98 (d, 2H), 2.87 (d, 3H);MS (EI) for C₂₂H₂₀N₆O: 385.2 (MH⁺).

3-amino-6-{1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]isoquinolin-7-yl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.07 (s, 1H), 8.89 (m, 2H), 8.59 (d, 1H),7.90 (d, 1H), 7.79 (d, 2H), 7.66 (br s, 2H), 7.28 (m, 1H), 7.25 (m, 1H),7.21 (t, 1H), 7.14 (t, 1H), 6.97 (d, 1H), 6.02 (m, 1H), 3.04 (m, 1H),2.91 (m, 1H), 2.85 (d, 3H), 2.61 (m, 1H), 2.07 (m, 1H); MS (EI) forC₂₄H₂₂N₆O: 411.2 (MH⁺).

3-amino-6-{3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,3-dihydro-1H-inden-5-yl}-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d₆-DMSO): 8.77 (s, 1H), 8.73 (m, 1H), 8.01 (m, 2H),7.57 (br s, 2H), 7.48 (m, 1H), 7.37 (m, 1H), 7.29 (d, 1H), 7.21 (m, 1H),7.15 (m, 2H), 4.34 (m, 2H), 2.97 (m, 2H), 2.84 (d, 3H), 2.77 (m, 2H),2.44 (m, 1H), 2.34 (m, 1H), 1.83 (m, 2H); MS (EI) for C₂₄H₂₅N₅O: 400.2(MH⁺).

3-amino-N-methyl-6-[3-({[2-(phenylamino)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamidewas synthesized according to the procedure described in above fromN-phenylethane-1,2-diamine and3-{5-amino-6-[(methylamino)carbonyl]pyrazine-2-yl}benzoic acid. Yield45%: 1H NMR (400 MHz, CDCl₃): 8.90 (s, 1H), 8.82 (br d, 1H), 8.70 (br t,1H), 8.45 (br s, 1H), 8.32 (br d, 1H), 7.82 (br d, 1H), 7.52 (t, 1H),7.02 (t, 2H), 6.62 (d, 2H), 6.50 (t, 1H), 5.72 (br t, 1H), 3.52 (d, 2H),3.20 (d, 2H), 2.92 (d, 3H); MS (EI) for C₂₁H₂₂N₆O₂: 391 (MH⁺)

6,6′-[(Oxomethanediyl)bis(iminobenzene-3,1-diyl)]bis(3-amino-N-methylpyrazine-2-carboxamide: To a solution of3-Amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide (0.10 g, 0.41mmol) in dry tetrahydrofuran were added triethylamine (46 mg, 0.45 mmol)and 4-nitrophenyl chloroformate (91 mg, 0.45 mmol). The reaction of wasallowed to stir overnight. A yellow solid material from the crudereaction was filtered and washed with diethyl ether (50 mL) and hexanes(50 mL) to yield6,6′-[(oxomethanediyl)bis(iminobenzene-3,1-diyl)]bis(3-amino-N-methylpyrazine-2-carboxamide(0.11 g, 54% yield): ¹H NMR (400 MHz, d₆-DMSO): 9.25 (br s, 2H), 8.75(br d, 2H), 8.70 (s, 2H), 8.01 (s, 2H), 7.74 (br d, 2H), 7.60 (br d,2H), 7.32 (t, 2H), 6.82 (br d, 2H), 2.80 (br s, 6H); MS (EI) forC₂₅H₂₄N₁₀O₃: 513 (MH⁺).

3-Amino-6-biphenyl-3-yl-N-methylpyrazine-2-carboxamide was synthesizedaccording to the procedure described in above. Yield 30%. ¹H NMR (400MHz, CDCl₃): 8.65 (br s, 1H), 8.03 (m, 1H), 8.01 (br s, 1H), 7.82 (dd,1H), 7.65 (m, 3H), 7.50 (m, 3H), 7.40 (t, 1H), 3.02 (br s, 3H; MS (EI)for C₁₈H₁₆N₄O: 305 (MH⁺)

Ethyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamatewas synthesized according to the procedure described in above from3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide and ethylchloroformate. Yield 55%: ¹H NMR (400 MHz, d₆-DMSO): 9.60 (br s, 1H),8.68 (br s, 2H), 8.12 (br s, 1H), 7.80 (d, 1H), 7.52 (d, 1H), 7.39 (t,1H), 4.06 (q, 2H), 2.85 (br s, 3H), 1.24 (t, 3H); MS (EI) forC₁₅H₁₇N₅O₃: 316 (MH⁺)

3-Amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide. To a solutionof 3-amino-6-bromo-N-methyl-2-pyrazinecarboxamide (1.23 g, 5.30 mmol) inN,N-dimethylformamide (30 mmol) were added[1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complexwith dichloromethane (1:1, 433 mg, 0.53 mmol), 3-aminophenylboronic acid(1.15 g, 7.41 mmol), and triethylamine (1.07 g, 10.6mmol). The solutionwas degassed with nitrogen 3-5 min. The reaction was heated at 85-90° C.for 15 h with stirring. The reaction was allowed to cool to roomtemperature and diluted with ethyl acetate (400 mL). The organic layerwas washed with saturated aqueous sodium bicarbonate (50 mL), saturatedaqueous sodium chloride (50 mL), dried over magnesium sulfate, filtered,and concentrated to give crude product. To the crude product was added4.0 N hydrochloric acid (1,4-dioxane solution, 30 mL). The resultingsolid was filtered and washed with diethyl ether/methanol (4:1). Thesolid was dissolved in methanol and neutralized with sufficient AG 1-X8Resin (hydroxide form) that the pH of the solution became basic. Themixture was filtered, and the filtrate was concentrated on a rotaryevaporator at reduced pressure to afford3-Amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide (0.70 g, 54%yield) as dark green solid. ¹H NMR (400 MHz, d₆-DMSO): 8.70(br s, 1H),8.62 (s, 1H), 7.60 (br s, 2H), 7.25 (m, 2H), 7.10 (t,. 1H), 6.15 (d,1H), 5.06 (s, 2H), 2.8 (br s, 3H); MS (EID for C₁₂H₁₃N₅O: 244 ).

Example 18

Scheme 9 depicts a general synthetic route for compounds of theinvention having substituents -W-X-Y according to formula I, wherein,for example, W is phenylene, X is —CH₂NH—, and Y is an indanyl group.Note, as defined above any of W, X, or Y are optionally substituted;this is only a set of examples. As depicted, intermediate (xxxix) isincorporated into a compound of the invention, (xliv). For example,optionally substituted indanone (xxxix) was to the corresponding alcohol(xl) using sodium borohydride or other appropriate reducing agent,depending upon, among other things, the substituent, R. The alcoholgroup in (xl) is transformed into an azide group in (xli) usingdiphenylphosphoryl azide and 1,8-diazabicyclo{5.4.0]undec-7-ene (DBU),for example. Reduction of azide (xli) is carried out typically, but notnecessarily, using tin chloride give amine (xlii). Amine (xlii) iscoupled to aldehyde (xliii), via reductive amination to afford (xliv).Amine (xlii) could also be coupled to a benzyl bromide, analogous toaldehyde (xxxxiii) to form (xliv), for example.

3-amino-N-methyl-6-[3-({[5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]aminomethyl) phenyl]pyrazine-2-carboxamide

5-(2-thienyl)-2,3-dihydro-1H-inden-1-one. To a solution of5-bromo-1-indanone (0.52g, 2.5 mmol) in toluene (5 mL) were addedtetrakis(triphenylphosphine)-palladium(0) (29 mg, 0.03 mmol),thiophene-2-boronic acid (0.48 g, 3.7 mmol), ethanol (5 mL), and 2.0 Nsodium carbonate (3 mL). The solution was flushed with nitrogen for 3minutes. The reaction was heated at 110-120° C. for 4 h. Reaction cooledto room temperature and diluted with ethyl acetate (200 mL). The organiclayer was washed with saturated aqueous sodium bicarbonate (2×50 mL),water (40 mL), saturated aqueous sodium chloride (50 mL), dried overmagnesium sulfate, filtered and concentrated to afford5-(2-thienyl)-2,3-dihydro-1H-inden-1-one (0.50g, 94% yield) as puresolid product. ¹H NMR (400 MHz, CDCl₃) 7.80 (d, 1H), 7.70 (s, 1H), 7.62(d, 1H), 7.43 (dd, 1H), 7.38 (dd, 1H), 7.12 (m, 1H), 3.20 (m, 2H), 2.66(m, 2H).

5-(2-thienyl)-2,3-dihydro-1H-inden-1-ol: To a slurry of sodiumborohydride (0.22 g, 5.86 mmol) in methanol (6mL) at 0° C. was added asolution of 5-(2-thienyl)-2,3-dihydro-1H-inden-1-one (0.50 g, 2.34 mmol) in methanol (2 mL). The reaction was slowly warmed to room temperatureand stirred until the reaction was completed as monitored by thin layerchromatography (4 h). The reaction mixture was carefully quenched with1.0 N aqueous hydrochloric acid at 0° C. until a clear solution wasobtained. Diluted with ethyl acetate (200 mL), washed with saturatedaqueous sodium bicarbonate, saturated aqueous sodium chloride (brine),and dried over anhydrous magnesium sulfate. Filtration, concentrationand column chromatography on silica (7:3 hexanes/ethyl acetate) gave5-(2-thienyl)-2,3-dihydro-1H-inden-1-ol (0.30 g, 59% yield) as solid. ¹HNMR (400 MHz, CDCl₃): 7.48 (m, 2H), 7.38 (br d, 1H), 7.26 (m, 2H), 7.08(dd, 1H), 5.21 (t, 1H), 3.04 (m, 1H), 2.80 (m, 1H), 2.50 (m, 1H), 2.10(brs, 1H), 1.93 (m, 1H).

2-(1-azido-2,3-dihydro-1H-indene-5-yl)thiophene: To a solution of5-(2-thienyl)-2,3-dihydro-1H-inden-1-ol (0.30 g, 1.39 mmol) intetrahydrofuran (6 mL ) was added diphenylphosphoryl azide (0.58 g, 2.10mmol) at 0° C. The reaction was stirred for 5 min prior to the additionof 1,8-diazabicyclo{5.4.0]undec-7-ene (DBU, 0.32 g, 2.10 mmol). Thereaction was further stirred for 15 min at 0° C. before the reaction wasallowed to warm to room temperature. The reaction was stopped after 1 hwhen the reaction was completed as monitored by thin layerchromatography. Diluted with ethyl acetate (200 mL), washed with water,saturated aqueous sodium chloride (brine), and dried over anhydrousmagnesium sulfate. Filtration, concentration and column chromatographyon silica (7:3 hexanes/ethyl acetate) gave2-(1-azido-2,3-dihydro-1H-indene-5-yl)thiophene (0.24g, 72% yield) asoil. ¹H NMR (400 MHz, CDCl₃) 7.54 (m, 2H), 7.40 (m, 2H), 7.24 (m, 1H),7.08 (m, 1H), 5.85 (t, 1H), 3.12 (m, 1H), 2.90 (m, 1H), 2.45 (m, 1H),2.19 (m, 1H).

5-(2-thienyl)-2,3-dihydro-1H-indene-1-yl)amine: To a solution of2-(1-azido-2,3-dihydro-1H-indene-5-yl)thiophene (0.24 g, 0.99 mmol) inmethanol (2mL) was added solid tin chloride dihydrate (0.45 g, 1.99mmol) at room temperature under nitrogen. The reaction was stirred atroom temperature overnight. The crude reaction mixture was poured into aseparatory funnel and diluted with ethyl acetate (250 mL). The organiclayer was washed with 2.0 N aqueous sodium hydroxide (50 mL), saturatedaqueous sodium chloride (brine), and dried over anhydrous magnesiumsulfate. Filtration, concentration and column chromatography on silica(9:1 dichloromethane/methanol) gave[5-(2-thienyl)-2,3-dihydro-1H-indene-1-yl]amine (0.15 g, 72% yield) assemi-solid: ¹H NMR (400 MHz, CDCl₃) 7.54 (m, 1H), 7.40 (d, 2H), 7.29 (m,2H), 7.08 (m, 1H), 4.40 (t, 1H), 3.05 (m, 1H), 2.90 (m, 1H), 2.56 (m,1H), 1.80 (m, 1H).

3-amino-N-methyl-6-[3-({[5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:To a solution of 5-(2-thienyl)-2,3-dihydro-1H-indene-1-yl]amine (73 mg,0.34 mmol) in acetonitril (3 mL) were added3-amino-6-[3-(bromomethyl)phenyl]-N-methylpyrazine-2-carboxamide (41 mg,0.13 mmol) and N,N-diisopropylethylamine (22 mg, 0.17 mmol) at roomtemperature. The reaction was stirred overnight. Diluted with ethylacetate (100 mL) and washed with water, saturated aqueous sodiumchloride (brine), and dried over anhydrous magnesium sulfate. Filtrationand concentration and column purification on silica (9:1 ethylacetate/methanol) gave3-amino-N-methyl-6-[3-({[5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide(30 mg, 51% yield) as yellow solid. ¹NMR (400 MHz, CD₃OD): 8.70 (s, 1H),8.15 (br s, 1H), 7.86 (d, 1H), 7.49 (m, 6H), 7.32 (m, 2H), 7.05 (m, 1H),4.35 (m, 1H), 3.92 (d, 2H), 3.10 (m, 4H), 2.95 (s, 3H), 2.85 (m, 1H),2.45 (m, 1H), 2.10 (m, 1H); MS (EI) for C₂₆H₂₅N₅OS: 456 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹NMR (400 MHz, d₆-DMSO): 9.80 (br s, 2H), 9.40 (br S, 1H), 8.84 (s, 1H),8.80 (s, 1H), 8.25 (d, 1H), 7.88 (br s, 1H), 7.80 (d, 1H), 7.48 (m, 4H),4.82 (s, 1H), 4.24 (s, 2H), 3.25 (s, 3H), 3.20 (m, 1H), 2.80 (m, 1H),2.50 (m, 1H), 2.40 (m, 1H); MS (EI) for C₂₂H₂₂N₅OBr: 453,455 (MH⁺).

3-amino-6-(3-{[(5-furan-2-yl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹NMR (400 MHz, CD₃OD): 8.65 (s, 1H), 8.15 (s, 1H), 7.88 (d, 1H), 7.50(m, 6H), 6.70 (d, 1H), 6.45 (m, 1H), 4.40 (m, 1H), 4.01 (d, 2H), 3.15(m, 3H), 2.96 (s, 3H), 2.85 (m, 1H), 2.50 (m, 1H), 2.45 (m, 1H), 2.10(m, 1H); MS (EI) for C₂₆H₂₅N₅O₂: 440 (MH⁺).

3-amino-6-(3-{[(5-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹NMR (400 MHz, CDCl₃): 8.58 (s, 1H), 8.20 (br s, 1H), 8.08 (br s, 1H),7.70 (d, 1H), 7.40 (m, 3H), 7.20 (s, 1H), 7.15 (d, 1H), 4.40 (m, 1H),3.80 (s, 2H), 3.10 (m, 4H), 2.80 (s, 1H), 2.45 (m, 1H), 2.20 (m, 1H); MS(EI) for C₂₂H₂₂N₅OCl: 408 (ME+).

3-amino-6-(3-{[(5-furan-3-yl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹NMR (400 MHz, CDCl₃): 8.62 (br s, 1H), 8.05 (br s, 1H), 7.89 (br s,1H), 7.78 (m, 2H), 7.40 (m, 6H), 6.70 (br s, 1H), 4.35 (m, 1H), 4.01 (d,1H), 3.10 (m, 4H), 2.95 (s, 3H), 2.85 (m, 1H), 2.50 (m, 1H), 1.85 (m,1H); MS (EI) for C₂₆H₂₅N₅O₂: 440 (MH+).

3-amino-N-methyl-6-[3-({[5-(3-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:1NMR (400 MHz, CDCl₃ ): 8.64 (s, 1H), 8.02 (br s, 1H), 7.90 (br s, 1H),7.78 (m, 1H), 7.44 (m, 6H), 7.38 (m, 2H), 4.40 (m, 1H), 4.02 (d, 2H),3.15 (m, 4H), 2.90 (m, 1H), 2.50 (m, 1), 1.90 (m, 1H); MS (EI) forC₂₆H₂₅N₅OS: 456 (MH+).

3-amino-N-methyl-6-(3-{[(5-phenyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide:1NMR (400 MHz, 46-DMSO ): 8.82 (m, 2H), 8.16 (br s, 1H), 8.05 (d, 1H),7.62 (d, 2H), 7.45 (m, 7H), 7.34 (m, 1H), 4.24 (m, 1H), 3.90 (m, 2H),3.01 (m, 1H), 2.80 (m, 4H), 2.38 (m, 1H), 1.90 (m, 1H); MS (EI) forC₂₈H₂₇N₅O: 450 (MH+).

3-amino-N-methyl-6-[3-({[6-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino]methyl)phenyl]pyrazine-2-carboxamide:¹NMR (400 MHz, CDCl₃): 8.60 (s, 1H), 7.99 (br s, 1H), 7.88 (br s, 1H),7.75 (m, 1H), 7.60 (s, 1H), 7.45 (m, 3H), 7.24 (m, 3H), 7.04 (m, 1H),4.40 (m, 1H), 4.02 (d, 2H), 3.08 (m, 4H), 2.83 (m, 1H), 2.50 (m, 1H),1.86 (m, 1H); MS (EI) for C₂₆H₂₅N₅O S: 456 (MH+).

3-amino-N-methyl-6-[3-({[5-(4-methyl-2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:1NMR (400 MHz, CDCl₃): 8.60 (s, 1H), 8.01 (br s, 1H), 7.88 (br s, 1H),7.74 (m, 1H), 7.60 (s, 1H), 7.40 (m, 5H), 7.08 (br, s 1H), 6.80 (br s,1H), 4.70 (m, 1H), 4.02 (d, 2H), 3.06 (m, 4H), 2.85 (m, 1H), 2.50 (s,3H), 1.90 (m, 1H); MS (EI) for C₂₇H₂₇N₅OS: 470 (MH+).

3-amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:1NMR (400 M, CDCl₃): 8.60 (s, 1H), 8.15 (br s, 1H), 7.88 (br 1H), 7.65(d, 1H), 7.40 (m, 3H), 7.26 (d, 1H), 6.96 (t, 1H), 6.90 (d, 1H), 4.60(m, 3H), 3.90 (m, 2H), 3.01 (m, 3H); MS (EI) for C₂₁H₂₁N₅O₂: 376 (MH+).

3-amino-N-methyl-6-[3-({[5-(4-methylphenyl)-2,3-dihydro-1H-inden-1-yl]amino}miethyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.80 (br s, 1H), 9.02 (d, 1H), 8.82 (s, 1H),8.60 (s, 1H), 8.21 (d, 1H), 7.50 (m, 7H), 7.25 (d, 1H), 4.82 (m, 1H),4.30 (m, 2H), 3.20 (m, 1H), 2.92 (m, 1H), 2.80 (d, 3H), 2.50 (m, 1H),2.30 (s, 3H), 2.40 (m, 1H); MS (EI) for C₂₉H₂₉N₅O: 464 (MH+).

Example 19

Scheme 10 depicts a general synthetic route for compounds of theinvention having substituents —W—X—Y according to formula I, wherein,for example, W is phenylene, X is —CH₂NR ⁴—, and Y is various groups.Note, as defined above any of W, X, or Y are optionally substituted;this is only a set of examples. As depicted, primary amine (xlv), whichin this example incorporates Y, is incorporated into a compound of theinvention, (1). For example, amine (xlv), which has Y as part of itsstructure for example, is converted to 2,4-dinitrosulfonamide (xlvi).Sulfonanide (xlvi) is used to make sulfonamide (xlvii). Thetransformation (xlvi) to (xlvii) is carried out either under alkylation(R⁴L₃, where -L₃ is a leaving group) or Mitsunobu (R⁴OH) conditions. Thesulfonamide bond is cleaved, typically but not necessarily via additionof a primary amine e.g. nt-propyl amidne, to free secondary amine(xlviii), which has Y and R⁴ as part of its structure. Amine (xlviii)was then incorporated into compounds of the invention, typically but notnecessarily, via coupling to a benzyl bromide, for example (xlix), tomake compound (1).

3-amino-6-[3-({[(2S)-6-bromo-1,2,34-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide

N-[(S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]-2,4-dinitrobenzenesulfonamide:To a solution of (S)-6-bromo-2-aminotetraline (0.20 g, 0.9 mmol) intetrahydrofuran (2 mL) was added N,N-diisopropylethylamine at 0° C. Asolution of 2,4-dinitrobenzenesulfonyl chloride (0.29 g, 1.1 mmol) intetrahydrofuran (2 mL) was added slowly via a syringe. The reaction wasallowed to warm to room temperature and further stirred until thecompletion of the reaction (30 min) as monitored by thin layerchromatography. The crude reaction mixture was poured into a separatoryfunnel and diluted with ethyl acetate (250 mL) and washed with water (30mL), saturated aqueous sodium chloride (40 mL), and dried over anhydrousmagnesium sulfate. Filtration and concentration afforded the crudeproduct. A pureN-[(2S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]-2,4-dinitrobenzenesulfonamide(0.28 g, 70% yield) was separated from trituration with ether/hexane(5:1, 30 mL) as a yellow solid. ¹NMR (400 MHz, CD₃OD): 8.75 (s, 1H),8.60 (dd, 1H), 8.38 (d, 1H), 7.22 (br s, 1H), 7.20 (d, 1H), 6.90 (d,1H), 3.65 (m, 1H), 2.65 (m, 4H), 1.90 (m, 1H), 1.75 (m, 1H).

3-Amino-6-[3-({[(2S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]amino]methyl)phenyl]-N-methylpyrazine-2-carboxamide:To a solution ofN-[(2S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]-2,4-dinitrobenzenesulfonamide(68 mg, 0.15 mmol) in N,N-dimehtylformamide (1 mL) were added solidpotassium carbonate (0.10 g, 0.75 mmol) and3-amino-6-[3-(bromomethyl)phenyl]-N-methylpyrazine-2-carboxamide (70 mg,0.22 mmol). The reaction stirred overnight at room temperature anddiluted with ethyl acetate (50 mL). The organic layer was washed withwater (30 mL) and saturated aqueous sodium chloride (30 mL), and driedover magnesium sulfate. Filtration and concentration gave crude productthat was used in the next step without any purification.

To the dichloromethane solution (2 mmol) of the above product was addedexcess n-propylamine (0.5 mL) and stirred for 30 min. The organicsolvent and excess reagent were removed at reduced pressure. Columnpurification on silica (9:1, ethyl acetate/methanol) gave an oilyproduct.

To a solution of the above product in methanol (2 mL) was added 4.0 Nhydrochloric acid (1,4-dioxane solution, 1.50 mL) and stirred for 40min. Evaporation of the excess reagent and solvent, washing with diethylether afforded3-amino-6-[3-(([(2S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide(16 mg, 23% yield) as hydrochloric acid salt. ¹NMR (400 MHz, CDCl₃):8.62 (s, 1H), 8.02 (br s, 1H), 7.82 (br s, 1H), 7.75 (d, 1H), 7.40 (m,2H), 7.20 (m, 2H), 6.74 (d, 1H), 4.01 (m, 2H), 2.90 (m, 6H), 2.60 (m,2H), 2.12 (m, 1H), 1.70 (m, 1H); MS (EI) for C₂₃H₂₄N₅OBr: 466 (MH+).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-6-[3-({[(2R)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]amino]methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹NMR (400 MHz, CDCl₃): 8.60 (s, 1H), 8.05 (br s, 1H), 7.83 (br s, 1H),7.75 (d, 1H), 7.42 (m, 2H), 7.20 (m, 2H), 6.72 (d, 1H), 4.01 (m, 2H),3.10 (m, 4H), 2.84 (m, 2H), 2.60 (m, 1H), 2.10 (m, 1H), 1.70 (m, 2H); MS(EI) for C₂₃H₂₄N₅OBr: 466 (MH⁺).

3-amino-6-{3-[(cyclopentylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide: ¹NMR (400 MHz, CDCl₃): 8.70 (s, 1H),8.48 (br s, 1H), 8.16 (d, 1H), 7.58 (m, 3H), 4.30 (s, 2H), 3.04 (br s,3H), 2.20 (m, 2H), 1.72 (m, 7H); MS (EI) for C₁₈H₂₃N₅O: 326 (MH⁺).

3-amino-N-methyl-6-{3-[({(1S,2S)-2-[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide: ¹NMR (400 MHz, CDCl₃): 8.60 (s,1H), 8.06 (br s, 1H), 7.80 (br s, 1H), 7.74 (d, 1H), 7.40 (t, 2H), 7.32(m, 6H), 4.50 (q, 2H), 3.85 (m, 3H), 3.20 (m, 1H), 3.01 (d, 3H), 2.01(m, 1H), 2.10 (m, 2H), 1.73 (m, 4H), 1.42 (m, 1H); MS (EI) forC₂₅H₂₉N₅O₂: 432 (MH⁺).

3-amino-N-methyl-6-{3-[({(1R,2R)-2-[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹NMR (400 MHz, CDCl₃): 8.65 (s, 1H), 8.40 (br s, 1H), 8.12 (d, 1H), 7.58(t, 1H), 7.48 (d, 1H), 7.34 (m, 5H), 4.60 (q, 2H), 4.32 (s, 2H), 4.28(m, 1H), 3.60 (m, 1H), 3.02 (s, 3H), 2.30 (m, 1H), 2.15 (m, 1H), 1.83(m, 4H); MS (EI) for C₂₅H₂₉N₅O₂: 432 (MH⁺).

Example 203-Amino-6-[3-({[2-(dimethylamino)-1-phenylethyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide

To a solution of (2-amino-2-phenethyl)dimethyl amine (200 mg , 1.22mmol) in acetonitril (15 mL ) were added3-amino-6-[3-(bromomethyl)phenyl]-N-methylpyrazine-2-carboxamide (0.11g, 0.35 mmol) and N,N-diisopropylethyl amine (0.14 g, 1.05 mmol) at roomtemperature. The reaction was stirred overnight. Diluted with ethylacetate (100 mL), washed with water (30 mL), saturated aqueous sodiumchloride (brine), and dried over anhydrous magnesium sulfate. Filtrationand concentration and reverse phase HPLC purification gave a trifluoroacetate salt. The fraction from the HPLC was neutralized with saturatedaqueous sodium bicarbonate (50 mL) and diluted with ethyl acetate (200mL). The organic layer was washed saturated aqueous sodium chloride (30mL), dried over anhydrous magnesium sulfate, filtered, and concentratedto give the free amine. This free amine was converted into hydrochloricacid salt by treatment with 4.0 N hydrochloric acid (1,4-dioxanesolution, 2.0 mL) in methanol solution (3 mL). Evaporation of the excessreagent and solvent gave3-amino-6-[3-({[2-(dimethylamino)-1-phenylethyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide(88 mg, 18% yield) as yellow solid: 1NMR (400 MHz, CDCl₃): 8.61 (s, 1H),8.05 (br s, 1H), 7.78 (br s, 1H), 7.74 (d, 1H), 7.35 (br m, 7H), 3.85(d, 1H), 3.75 (dd, 1H), 3.60 (d, 1H), 3.04 (s, 3H), 2.65 (m, 2H), 2.20(s, 6H); MS (EI) for C₂₃H₂₈N₆O: 405 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-N-methyl-6-(3-{[(2-morpholin-4-yl-1-phenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide:1NMR (400 MHz, CDCl₃): 8.60 (s, 1H), 8.02 (br s, 1H), 7.74 (d, 1H), 7.70(s, 1H), 7.39 (br m, 7H), 3.88 (d, 1H), 3.78 (dd, 1H), 3.65 (m, 3H),3.58 (s, 1H), 3.05 (d, 3H), 2.55 (t, 1H), 2.45 (m, 2H), 2.30 (m, 3H); MS(EI) for C₂₅H₃₀N₆O₂: 447 (MH⁺).

3-amino-N-methyl-6-(3-{[(1-phenyl-2-pyrrolidin-1-ylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹NMR (400 MHz, CDCl₃): 8.60 (s, 1H), 8.12 (br s, 1H), 7.80 (s, 1H), 7.74(d, 1H), 7.40 (br m, 5H), 7.30 (m, 2H), 3.82 (d, 1H), 3.74 (d, 1H), 3.60(d, 1H), 3.05 (d, 3H), 2.90 (m, 2H), 2.70 (br s, 1H), 2.50 (m, 1H), 2.40(m, 1H), 2.25 (dd, 2H), 1.70 (m, 4H); MS (EI) for C₂₅H₃₀N₆O: 431 (MH⁺).

Example 213-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-hydroxyethyl)pyrazine-2-carboxamide

To a solution of methyl3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-hydroxyethyl)pyrazine-2-carboxylate(30 mg, 08 mmol) in methanol (1 mL) was added ethanolamine (20 mg, 0.32mmol). The reaction was heated at 80-90° C. overnight. The reactioncooled to room temperature and diluted with ethyl acetate (150 mL). Theorganic layer was washed with saturated aqueous sodium bicarbonate andsaturated aqueous sodium chloride, and dried over magnesium sulfate.Filtration, concentration, and column purification on silica (9.5:0.5,dichloromethane/methanol) afforded free amine product. To a solution ofthe amine in diethyl ether (2 mL) was added 4 N hydrochloric acid(1,4-dioxane solution, 1 mL) and stirred for 30 min. Concentration andwashings with diethyl ether afforded3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-hydroxyethyl)pyrazine-2-carboxamide(13 mg, 38% yield) as yellow hydrochloric acid salt. 1NMR (400 MHz,CDCl₃): 8.58 (s, 1H), 8.40 (br s, 1H), 7.90 (br s, 1H), 7.68 (m, 1H),7.38 (m, 3H), 7.20 (m, 3H), 4.35 (t, 1H), 3.90 (d, 2H), 3.80 (t, 2H),3.60 (m, 2H), 3.06 (m, 1H), 2.84 (m, 1H), 2.48 (m, 3H), 1.92 (m, 1H); MS(EI) for C₂₃H₂₅N₅O₂: 404 (MH+).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-N-cyclopropyl-6-(3-([(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide:1NMR (400 MHz, CDCl₃): 8.60 (s, 1H), 8.05 (br s, 1H), 7.83 (br s, 1H),7.70 (m, 1H), 7.40 (m, 3H), 7.20 (m, 3H), 4.35 (t, 1H), 4.02 (d, 2H),3.02 (m, 1H), 2.85 (m, 2H), 2.50 (m, 1H), 1.92 (m, 1H), 1.13 (m, 1H),0.90 (m, 2H), 0.70 (m, 1H); MS (EI) for C₂₄H₂₅N₅O: 400 (MH+).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino)methyl}phenyl)-3-(pyrrolidin-1-ylcarbonyl)pyrazin-2-amine:1NMR (400 MHz, CDCl₃): 8.57 (s, 1H), 7.95 (br s, 1H), 7.78 (m, 1H), 7.42(m, 3H), 7.24 (m, 3H), 4.35 (t, 1H), 4.02 (d, 4H), 3.70 (m, 2H), 3.05(m, 1H), 2.85 (m, 1H), 2.48 (m, 1H), 1.94 (m, 5H); MS (EI) forC₂₅H₂₇N₅O: 414 (MH+).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-hydroxypropyl)pyrazine-2-carboxamide:¹NMR (400 MHz, CDCl₃): 9.56 (s, 1H), 8.65 (m, 1H), 8.38 (br s, 1H), 7.72(d, 1H), 7.38 (t, 2H), 7.50 (m, 4H), 4.40 (t, 1H), 4.01 (q, 2H), 3.60(m, 3H), 3.40 (m, 1H), 3.08 (m, 1H), 2.90 (m, 1H), 2.50 (m, 1H), 2.00(m, 1H), 1.75 (m, 2H); MS (EI) for C₂₄H₂₇N₅O₂: 418 (MH+).

Example 223-amino-6-(3-{(1S)-1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]ethyl}phenyl)-N-methylpyrazine-2-carboxamide

N-[(1S)-1-(3-bromophenyl)ethyl]-2,4-dinitrobenzenesulfonamide: To astirred ice-cooled solution of (S)-(−)-3-bromo-α-methylbenzylamine (832mg, 4.16 mmol, from Chiragene) in 15.6 mL of THF was added 1.33 g (4.99mmol, 1.20 eq.) of 2,4-dinitrobenzenesulfonyl chloride, followed by 1.08mL (6.20 mmol, 1.49 eq.) of N,N-diisopropylethylamine. The ice bath wasremoved, and the mixture was stirred at room temperature for 19 h andthen concentrated. The residue was taken up in EtOAc, washed with 2×H₂O,dried over Na₂SO₄, filtered, and concentrated. The residue was sonicatedin ca. 5 mL of EtOAc until a precipitate was formed. The mixture wasdiluted to ca. 25 mL with hexanes. Filtration afforded product as a tansolid (1.69 g, 94.4% yield).

N-[(1S)-1-(3-bromophenyl)ethyl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dinitrobenzenesulfonamide:A flask was charged with 500 mg (1.16 mmol) ofN-[(1S)-1-(3-bromophenyl)ethyl]-2,4-dinitrobenzenesulfonamide, 625 mg(4.66 mmol, 4.02 eq.) of (R)-(−)-1-indanol (from Sigma-Aldrich), 305 mg(1.16 mmol, 1.0 eq.) of triphenylphosphine, 6.75 mL of benzene and themixture cooled on an ice-water bath. To the mixture was added 0.183 mL(1.16 mmol, 1.0 eq.) of diethyl azodicarboxylate (DEAD). The ice bathwas removed, and stirring was continued for 1 h. The mixture was cooledon an ice-water bath, followed by addition of 305 mg (1.16 mmol, 1.0eq.) of triphenylphosphine and 0.183 mL (1.16 mmol, 1.0 eq.) of DEAD.The ice bath was removed, and stirring continued for 1 h. The mixturewas cooled on an ice-water bath, followed by a third addition of 305 mg(1.16 mmol, 1.0 eq.) of triphenylphosphine and 0.183 mL (1.16 mmol, 1.0eq.) of DEAD. The ice bath was removed, and stirring continued for 1 h.The mixture was diluted with EtOAc, washed with 2×sat. aqueous NaCl,dried (Na₂SO₄), filtered, and concentrated. The crude material waspurified by silica gel chromatography on a 30 mm column (3.5 inches ofsilica) using EtOAc as eluent. The product was triturated in 10% EtOAcin hexanes and filtered affording 625 mg (98.5% yield) of product as asolid.

(1S)-1-(3-bromophenyl)ethyl](1S)-2,3-dihydro-1H-inden-1-ylamine: To amixture of 625 mg (1.14 mmol) ofN-[(1S)-1-(3-bromophenyl)ethyl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dinitrobenzenesulfonamidein 11.5 mmol of CH₂Cl₂ was added 1.44 mmol (17.5 mmol, 15.4 eq.) ofn-propylamine. The reaction was stirred for 16 h at room temperature andconcentrated. The crude material was purified by silica gelchromatography on a 25 mm column (3.5 inches of silica gel) using 10%EtOAc in hexanes as eluent. After concentration, 4.0 mL of Et₂O wasadded to the residue, followed by 4 N HCl in dioxane. The mixture wassonicated, filtered, and washed with Et₂O. The material was taken up inEtOAc, washed with 2×sat. aqueous NaHCO₃, dried (Na₂SO₄), filtered, andconcentrated to afford 170 mg (47.2% yield) of product.

(1S)-N-{(1S)-1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl]ethyl}indane-1-aminewas synthesized according to the procedure described in above from[(1S)-1-(3-bromophenyl)ethyl](1S)-2,3-dihydro-1H-indene-1-ylamine andbis(pinacolato)diboron. Yield 64%. ¹H NMR (400 MHz, CDCl₃): 7.80 (br s,1H), 7.72 (br d, 1H), 7.58 (br d, 1H), 7.35 (m, 2H), 7.18 (m, 3H), 4.12(m, 2H), 2.90(m, 1H), 2.70 (m, 1H), 2.20 (m, 1H), 1.70 (m, 1H), 1.40 (d,3H), 1.24 (s, 12H).

3-amino-6-(3-{(1S)-1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]ethyl}phenyl)-N-methylpyrazine-2-carboxamidewas prepared according to the procedure described above by coupling(1S)-N-{(1S)-1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl]ethyl}indane-1-amineand 3-amino-6-bromo-N-methyl-2-pyrazincarboxamide as hydrochloric acidsalt. Yield 34%. ¹H NMR (400 MHz, CDCl₃): 8.64 (s, 1H), 8.15 (br s, 1H),8.02 (br s, 1H), 7.78 (m, 1H), 7.49 (m, 2H), 7.40 (m, 1H), 7.20 (m, 4H),4.21 (m, 2H), 3.02 (m, 4H), 2.78 (m, 1H), 2.22 (m, 1H), 1.80 (br s, 1H),1.42 (d, 3H); MS (EI) for C₂₃H₂₅N₅O: 388 (MH+).

Example 233-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)pyrazine-2-carboxcamide

3-bromo-N-[(1S)-2,3-dihydro-1H-indene-1-yl]benzenesulfonamide wassynthesized according to the procedure described above from(S)-1-aminoindan and 3-bromobenzensulfonyl chloride. Yield 52%. ¹H NMR(400 MHz, CDCl₃): 7.20 (m, 1H), 7.90 (dd, 1H), 7.80 (dd, 1H), 7.50 (t,1H), 7.20 (m, 2H), 7.15 (m, 1H), 7.02 br d, 1H), 4.80 (t, 1H), 2.90(m,1H), 2.70 (m, 1H), 2.20 (m, 1H), 1.70 (m, 1H).

N-[(1S)-2,3-dihydro-1H-inden-1-yl)]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)benzenesulfonamidewas synthesized according to the procedure described above from3-Bromo-N-[(1S)-2,3-dihydro-1H-indene-1-yl]benzenesulfonamide andbis(pinacolato)diboron. Yield 58%. ¹H NMR (400 MHz, CDCl₃): 8.40 (br s,1H), 8.02 (m, 2H), 7.54 (t, 1H), 7.16 (m, 4H), 4.90 (m, 1H), 4.70 (d,1H), 2.90 (m, 1H), 2.78 (m, 1H), 2.30 (m, 1H), 1.70 (m, 1H), 1.24 (s,12H).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)pyrazine-2-carboxamidewas prepared according to the procedure described above by couplingN-[(1S)-2,3-dihydro-1H-inden-1-yl)]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)benzenesulfonamide and 3-amino-6-bromo-N-methyl-2-pyrazincarboxamide.Yield 50%. ¹H NMR (400 Mz, d₆-DMSO): 8.86 (s, 1H), 8.60 (br s, 1H), 8.45(br d, 1H), 8.25 (br s, 1H), 8.20 (d, 1H), 7.85 (t, 2H), 7.70 (t, 1H),7.19 (m, 4H), 4.80 (m, 1H), 2.80 (m, 1H), 2.62 (m, 1H), 2.00 (m, 1H),1.60 (m, 1H); MS (EI) for C₂oH₁₉N₅O₃S: 410 (MH+).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamidewas prepared according to the procedure described above by couplingN-[(1S)-2,3-dihydro-1H-inden-1-yl)]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)benzenesulfonamideand tert-butyl3-[2-(3-amino-6-bromopyrazin-2-yl)-2-oxoethyl]piperidine-1-carboxylatefollowed by the deprotection of the boc group with 4.0 N hydrochloricacid(1,4-dioxane solution). Yield 50%. ¹H NMR (400 MHz, CD₃OD): 8.78 (brs, 1H), 8.58 (br s, 1H), 8.35 (d, 1H), 7.95 (d, 1H), 7.75 (t, 1H), 7.18(m, 2H), 7.10 (m, 2H), 4.85 (t, 1H), 4.30 (br s, 1H), 3.72 (m, 1H), 3.68(m, 1H), 3.55 (m, 1H), 3.50 (br d, 1H), 3.35 (dr d, 1H), 3.15 (br t,1H), 3.00 (br t, 1H), 2.90 (m, 1H), 2.70 (m, 1H), 2.10 (m, 2H), 1.78 (m,1H), 1.70 (m, 1H); MS (EI) for C₂₅H₂₈N₆O₃S: 493 (MH⁺).

N-[3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)phenyl]-2-(2,4-dichlorophenyl)acetamide:¹H NMR (400 MHz, CD₃OD): 8.52 (br s, 1H), 8.48 (br s, 1H), 7.82 (br d,1H), 7.48 (m, 6H), 7.35 (m, 1H), 3.92 (s, 3H), 3.70 (m, 1H), 3.42 (m,2H), 3.05 (m, 1H), 2.30 (m, 1H), 2.02 (m, 3H); MS (EI) for C₂₅H₂₄N₈OCl₂:524 (MH+).

1,1-dimethylethyl(3R)-3-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}pyrrolidine-1-carboxylate:¹H NMR (400 MHz; DMSO-D₆): 8.91 (s, 1H); 8.86 (m, 1H); 8.63 (d 1H); 8.45(s, 1H); 8.38 (d, 1H); 7.82 (d, 1H); 7.76 (t, 1H); 4.45 (m, 1H); 3.7-3.4(m, 4H); 2.85 (d, 3H); 2.33 (m, 1H); 1.9 (m, 1H); 1.4 (s, 9H); MS (EI)for C₂₂H₂₈N₆O₄: 441 (MH⁺)

Example 243-amino-N-methyl-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide

1,1-dimethylethyl-3-{[(3-{5-amino-6[(methylamino)carbonyl)pyrazin-2-yl}phenyl}carbonyl}amino}pyrrolidine-1-carboxylate (0.7 g,mmol) was suspended in dichloromethane (4 mL) and TFA (3 mL) was added.The mixture was stirred at ambient temperature for 2 hr. After removalof volatiles under reduced pressure, the residue was partitioned betweensaturated solution K₂CO₃ (300 mg) and dichloromethane (10 mL). Theorganic layer was separated, dried (Na₂SO₄) and evaporated to dryness toafford 0.4 g (74% yield) of3-amino-N-methyl-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide. ¹H NMR (400 MHz; DMSO-D₆): 8.9 (s, 1H); 8.85 (m,1H); 8.71 (d, 1H); 8.48 (m, 1H); 7.4 (d, 1H); 7.84 (d, 1H); 7.6 (t, 1H);4.54 (m, 2H); 3.6-3.18 (m, 4H); 2.85 (d, 3H); 2.25 (m, 1H); 2.1 (m, 1H);MS (EI) for C₁₇H₂₀N₆O₂: 341 (MH⁺)

3-{[(4-chlorophenyl)methyl]amino}-6-{3-[({(3R)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:To a solution of3-amino-N-methyl-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide(34.0 mg, 0.1 mmol) in acetonitrile was added K₂CO₃ (27.6 mg, 0.2 mmol)followed by 4-chlorobenzyl bromide (30.7 mg, 0.15 mmol). The mixture wasallowed to stir at room temperature over 12 h and filtered. Theacetonitrile solution was evaporated to dryness, the residue waschromatographed on silica gel using ethyl acetate/hexane 4:1 v/v andtrituration of the resulting solid with hexane afforded3-{[(4-chlorophenyl)methyl]amino}-6-{3-[({(3R)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide(28 mg, 47.6%yield): ¹H NMR (400 MHz; DMSO-D₆): 8.9 (s, 1H); 8.85 (m,1H); 8.75 (m, 1H); 8.38 (m, 2H); 7.78-7.5 (m, 1H); 4.63 (m, 5H); 3.9 (m,1H); 3.6 (m, 2H); 3.4 (m, 1H); 2.85 (d, 3H); 2.5 (m, 1H); 2.2 (m, 1H);MS (EI) for C₃₁H₃₀N₆O₂Cl₂: 589 (MH⁺)

The following compounds were prepared in an analogous manner as3-{[(4-chlorophenyl)methyl]amino}-6-{3-[({(3R)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide.

3-amino-6-{3-[({(3R)-1-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.92 (s, 1H); 8.86 (m, 1H); 8.6 (d, 1H); 8.46(m, 1H); 8.36 (d, 1H); 7.82 (d, 1H); 7.6-7.4 (m, 4H); 4.43 (m, 1H); 3.7(m, 2H); 2.9 (m, 1H); 2.88 (d, 3H); 2.75 (m, 1H); 2.58 (m, 2H); 2.2 (m,1H); 1.85 (m, 1H); MS (EI) for C₂₄H₂₄N₆O₂Cl₂: 4.99 (MH⁺)

N-methyl-3-({[3-(methyloxy)phenyl]methyl}amino)-6-(3-{[((3R)-1-{[3-(methyloxy)phenyl]methyl}pyrrolidin-3-yl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:8.98 (m, 1H); 8.92 (m, 1H); 8.88 (s, 1H); 8.48 (m, 1H); 8.38 (d, 1H);7.78 (d, 1H); 7.6-7.0 (m, 9H); 4.7 (m, 5H); 3.95 (m, 1H); 3.85 (s, 3H);3.74 (s, 3H); 3.7 (m, 2H); 3.54 (m, 1H); 2.85 (s, 3H); 2.45(m, 1H); 2.28(m, 1H); MS (EI) for C₃₃H₃₆N₆O₄; 581 (MH⁺)

3-Amino-6-{3-[({(3R)-1-[(2,6-dichlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.91 (s, 1H); 8.86 (m, 1H); 8.55 (d, 1H);8.46 (m, 1H); 8.38 (d, 1H); 7.82 (d, 1H); 7.6-7.3 (m, 4H); 4.4 (m, 1H);3.88 (s, 2H); 3.0 (m, 1H); 2.85 (d, 3H); 2.8-2.54 (m, 3H); 2.15 (m, 1H);1.85 (m, 1H); MS (EI) for C₂₄H₂₄N₆O₂C₂: 499 (MH⁺)

N-methyl-3-[(phenylmethyl)amino]-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.92 (m, 2H); 8.86 (s, 1H); 8.45 (s, 1H);8.36 (d, 1H); 7,76 (d, 1H); 7.7-7.46 (m, 11H); 4.65 (m, 5H); 3.91 (m,1H); 3.62 (m, 2H); 3.45 (m, 1H); 2.85 (d, 3H); 2.49 (m, 1H); 1.22 (m,1H); MS (EI) for C₃₁H₃₂N₆O₂: 521 (MH⁺)

1,1-dimethylethyl3-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino]methyl)pyrrolidine-1-carboxylate:¹H NMR (400 MHz; DMSO-D₆): 8.91 (s, 1H); 8.85 (m, 1H); 8.68 (m, 1H);8.46 (s, 1H); 8.38 (d, 1H); 7.82 (d, 1H); 7.56 (t, 1H); 3.4 (m, 5H); 3.0(m, 1H); 2.85 (d, 3H); 2.47 (m, 1H); 1.95 (m, 1H); 1.6 (m, 1H); 1.39 (s,9H); MS (EI) for C₂₃H₃₀N₆O₄: 455 (MH⁺)

1,1-dimethylethyl2-({[(3-{5-amino-6-[methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)pyrrolidine-1-carboxylate:¹H NMR (400 MHz; DMSO-D₆): 8.91 (s, 1H); 8.85 (m, 1H); 8.5 (m, 1H); 8.46(s, 1H); 8.38 (d, 1H);7.72 (d, 1H); 7.58 (t, 1H); 3.98 (m, 1H); 3.4 (m,4H); 2.85 (d, 3H); 1.85 (m, 4H); 1.39 (s, 9H); MS (EI) for C₂₃H₃₀N₆O₄:455 (MH⁺)

3-amino-N-methyl-6-(3-{[(pyrrolidin-3-ylmethyl)amino]carbonyl]phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.91 (s, 1H); 8.85 (m, 1H); 8.75 (m, 1H);8.66 (br s, 2H); 8.48 (s, 1H); 8.38 (d, 1H); 7.84 (d, 1H); 7.58 (t, 1H);3.6-3.2 (m, 5H); 3.1(m, 1H); 2.91 (m, 1H); 2.85 (d, 3H); 2.6 (m, 1H);2.0 (m, 1H); 1.7 (m, 1H); MS (EI) for C₁₈H₂₂N₆O₂: 355 (MH⁺)

3-amino-N-methyl-6-(3-{[(pyrrolidin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.91 (s, 1H); 8.85 (m, 1H); 8.5 (s, 1H); 8.4(d, 1H); 7.84 (d, 1H); 7.58 (t, 1H); 3.6-3.4(m, 3H); 3.1-3.2 (m, 2H);2.85 (d, 3H); 2.0-1.6 (m, 4H); MS (EI) for C₂₁H₂₁M₆O₂: 355 (MH⁺)

Example 25

Scheme 11 depicts a general synthetic route for compounds of theinvention having substituents —W—X—Y according to formula I, wherein,for example, W is phenylene, X is —C(—O)NHCH₂—, and Y is a3,4-dihydro-2H-benzo[1,4]oxazinyl group. As depicted, intermediate (li)is incorporated into a compound of the invention, (lvii). Nitro phenol(li) was reduced to aniline (lii). Then the aniline nitrogen wasacylated to give intermediate (liii). A ring closure was effected toyield intermediate (liv). Reduction of the cyano group gave (lv),followed by reduction of the carbonyl giving primary amine (lvi). Amine(lvi) was coupled to an acid to yield compounds of the invention, forexample (lvii) as depicted below.

3-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide

3-Amino-4-hydroxybenzonitrile: To a solution of3-nitro-4-hydroxybenzonitrile (3.28 g, 20 mmol) in ethyl acetate washydrogenated over 5% Pd/C, at an initial pressure 20 psi in a Parrshaker. After 3 h the reaction mixture was filtered (Celite). Thesolvent was removed under reduced pressure and the residue oil3-Amino-4-hydroxybenzonitrile (2.6 g, 97% yield) used in the next stepwithout further purification: ¹H NMR (400 MHz; DMSO-D₆): 6.85 (m, 2H);6.73 (d, 1H); 5.0 (br s, NH).

3-Oxo-3,4-dihydro-2H-1,4-benzoxazin-6-carbonitrile:3-amino-4-hydroxybenzonitrile (g, 10 mmol was dissolved in acetone (20mL) and water (20 mL) containing sodium bicarbonate (4 g).2-chloroacetyl chloride was added slowly and the mixture heated toreflux for 4 h and then allowed to stir overnight at 25 ° C. The layerswere separated, and the water layer was extracted with ethyl acetate.The organic layers were combined and evaporated to give3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-carbonitrile as an oil (1.3 g): ¹HNMR (400 M ; DMSO-D₆): 7.4 (d, 1H); 7.2 (s, 1H); 7.1 (d, 1H).

3,4-Dihydro-2H-1,4-benzoxazine-6-ylmethyl)amine: a solution of3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-carbonitrile (1.3 g ) in anhydrousTBF (20 mL) was slowly added to a stirred and ice -cooled solution oflithium aluminum hydride (30 mL, 1 M solution in THF). With continuedcooling water (5 mmol) and sodium hydroxide (5 mL, 20% solution), water(20 mL) and ethyl acetate (30 mL) were added in succession. The organicsolution was decanted from the white residue. The residue was washedtwice with ether, all the organic solution were combined then dried overanhydrous sodium sulfate. Filtration and concentration followed bydrying in vacuo afforded 3,4-dihydro-2H-1,4-benzoxazine-6-ylmethylamine(0.78 g,): ¹H NMR (400 MHz; DMSO-D₆): 6.52 (d, 1H); 6.49 (s, 1H); 6.37(d, 1H); 5.6 (br s, NH); 4.05 (t, 2H); 3.4 (m, 2H).

3-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 8.96 (t, 1H); 8.79 (s, 1H); 8.81 (m, 1H); 8.5(s, 1H); 8.35 (d, 1H)l 7.85 (d, 1H); 7.65 (br s, 2H); 7.55 (t, 1H); 6.55(m, 2H); 6.44 (d, 1H); 5.77 (s, 1H); 4.4 (d, 2H); 4.15 (m, 2H); 3.2 (s,1H); 2.85 (d, 3H); MS (EI) for C₂₂H₂₂N₆O₃: 419 (MH⁺)

Example 263-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pynolidin-2-yl]methylamino)carbonyl]phenyl}pyrazine-2-carboxamide

To a stirred solution of3-amino-N-methyl-6-(3-{[(pyrrolidin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide(35.4 mg, 0.01 mmol) and benzaldehyde (24.8 mg, 0.02 mmol) in methanol(3 mL) was added sodium cyanoborohydride (25 mg, 0.04 mmol). The mixturewas stirred for 1 h and then acetic acid added until the pH of thesolution was 7.0. The solution was stirred for an additional 6 h,solvent was removed and residue was partitioned with CHCl₃ and 2 Maqueous sodium hydroxide (5 mL). The aqueous phase was extracted withadditional CHCl₃ (2×5 mL) and the combined organic layer were washedwith saturated aqueous sodium chloride then dried over anhydrous sodiumsulfate. Filtration, concentration and column chromatography provided 10mg of3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz; CDCl₃); 8.7 (s, 1H); 8.65 (s, 1H); 8.28 (br s, 1H);7.95 (d, 1H); 7.22 (d, 1H); 7.53 (t, 1H); 7.2-7.4 (m, 5H); 4.3-3.5 (m,7H); 2.95 (d, 3H); 2.35-1.8 (m, 4H); MS (EI) for C25H₂₈N₆O₂: 445 )

3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-3-ylmethyl}amino)carbonyl]phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; CDCl₃): 8.67 (s, 1H); 8.42 (s, 1H); 8.15 (m, 1H); 7.95(d, 1H); 7.84 (d, 1H); 7.53 (t, 1H); 7.4 (m, 5H); 4.15 (m, 2H); 3.75 (m,1H); 3.4 (m, 2H); 3.0 (m, 5H); 2.22 (m, 1H); 1.95 (m, 1H); MS (EI) forC₂₅H₂₈N₆O₂: 445 (MH⁺)

3-amino-N-methyl-6-[3-({[(2-pyridin4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.1 (t, 1H); 8.6 (s, 1H); 8.84 (m, 1H); 8.64(m, 1H); 8.42 (m, 1H); 8.42 (m, 1H); 7.35 (d, 1H); 7.8 (d, 1H); 7.6-7.36(m, 6H); 7.28 (d, 1H) 4.43 (d, 2H); 2.85 (d, 3H); MS (EI) forC₂₅H₂₂N₆O₂: 439 (+)

Example 27

Scheme 12 depicts a general synthetic route for compounds of theinvention having substituents —W—X—Y according to formula I, wherein,for example, W is phenylene, X is —C(═O)NHCH₂—, and Y is a bis-aryl,aryl-heteroaryl, or heteroaryl-heteroaryl group. As depicted,intermediate (lvii), a compound of the invention, is converted to (lix),another compound of the invention, for example, via aromatic couplingreactions known in the art.

3-amino-N-methyl-6-[3-({[(2-pyridin-3-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-D₆): 9.1 (t, 1H); 8.6 (s, 1H); 8.64 (m, 1H); 8.58(m, 1H); 8.42 (s, 1H); 8.34 (d, 1H); 7.88 (m, 1H); 7.8 (d, 1H);7.58-7.34 (m, 5H); 7.28 (d, 1H) 4.43 (d, 2H); 2.85 (d, 3H); MS (I) forC₂₅H₂₂N₆O₂: 439 (MH⁺)

3-amino-N-methyl-6-[3-({[(4-pyridin-3-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:(400 MHz; CD₃OD): 8.24 (t, 1H); 9.08 (m, 1H); 8.78 (s, 1H); 8.72 (m,2H); 8.55 (m, 1H); 8.2 (d, 1H); 8.0 (m, 1H); 7.88 (d, 1H); 7.76 (m, 2H);7.58 (m, 3H); 4.54 (d, 2H); 2.85 (s, 3H); MS (EI) for C₂₅H₂₂N₆O₂: 439(MH⁺)

Example 283-amino-6-[3-(1H-benzimidazol-2-yl)phenyl]-N-methylpyrazine-2-carboxamide

3-Amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide: Methyl3-amino-6-(3-formylphenyl)pyrazine-2-carboxylate (0.6 g, mmol) wassuspended in ammonia (30 mL, 2.0 M solution in methyl alcohol) andbrought to reflux over 2 h, then water (100 mL) was added. The solid wascollected, treated with 4 M HCl in 1,4-dioxane (10 mL) and stirred at70° C. overnight. The solvent was removed and the residue waspartitioned with ethyl acetate and saturated sodium bicarbonate. Theorganic layer was washed with brine then dried over sodium sulfate.Filtration, concentration and column chromatography on silica afforded3-amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide (0.4 g).

3-amino-6-[3-(1H-benzimidazol-2-yl)phenyl]-N-methylpyrazine-2-carboxamide:A solution of 3-amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide(25.4 mg, 0.1 mmol) and 1,2-phenylendiamine in NMP (3 mL) was heated at80° C. for 8 h. The solvent was removed and the residue was trituratedwith 0.1 M aquous hydrochloric acid.

Filtration and hplc purification of the precipitate afforded (24 mg, 57%yield) of product: (400 MHz; DMSO-D₆): 8.9 (s, 1H); 8.85 (m, 1H); 8.8(s, 1H); 8.31 (d, 1H); 8.2 (d, 1H); 7.6 (m, 3H); 7.2 (m, 2H); 2.85 (d,3H); MS (EI) for C₁₉H₁₆N₆O: 345 (MH⁺)

Example 293-amino-N-methyl-6-[3-(4-phenyl-1H-imidazol-2-yl)phenyl]pyrazine-2-carboxamide

3-amino-6-{3-[amino(hydroxyimino)methyl]phenylpyrazine-2-carboxamide:3-Amino-6(3-cyanophenyl)-N-methylpyrazine-2-carboxamide (0.7 g, 2.76mmol) and hydroxylamine (5 ml, 50% aqueous) were stirred in methanol/THF(5 mL, 1:1) at 80° C. for 8 h. The mixture was poured into water (30mL). The solid was collected by filtration, washed with ethyl ether anddried to give3-amino-6-{3-[amino(hydroxyimino)methyl]phenylpyrazine-2-carboxamide(0.75 g, 94.9% yield) as a white solid: ¹H NMR (400 MHz; DMSO-d₆): 9.7(s, 1H); 8.85 (m, 2H); 8.3 (s, 1H); 8.2 (d, 1H); 7.74 (d, 1H); 7.4 (t,1H); 6.0 (s, 2H); 2.85 (d, 3H); MS (EI) for C₁₃H₁₄N₆O₂: 287 (MH⁺).

3-amino-6-{3-[amino(imino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:To a stirred solution of3-amino-6-{3-[amino(hydroxyimino)methyl]phenylpyrazine-2-carboxamide(0.858 mg, 3 mmol) in pyridine (5 mL) was added acetic anhydride (4mmol). The mixture was poured into water (50 mL) and extracted withethyl acetate (30 mL). The extract was washed with brine, dried(Na₂CO₃), and concentrate to provide6-{3-[(E,Z)-[(acetyloxy)imino](amino)methyl]phenyl}-3-amino-N-methylpyrazine-2-carboxamide:To a solution of this crude material (400 mg) in 950 mL of methanol wasadded Pd/C (5%, 20 mg) and the mixture was hydrogenated at 30 psi on aParr shaker. The mixture was filtered through celite and the filtratewas evaporated, and concentrated to provide (300 mg, 37% yield) of3-amino-6-{3-[amino(imino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:MS (EI) for C₁₃H₁₄N₆O: 271 (MH⁺).

3-amino-N-methyl-6-[3-(4-phenyl-1H-imidazol-2-yl)phenyl]pyrazine-2-carboxamide:To a stirred solution of3-amino-6-{3-[amino(imino)methyl]phenyl}-N-methylpyrazine-2-carboxamide(0.13 6 mg, 0.5 mmol) in DMF (5 mL) was added bronoacetophenone (0.11 g,0.55 mmol ) followed by K₂CO₃ (0.276 g). The resulting mixture washeated at 70 ° C. for 0.5 h. The mixture was poured into water (30 mL)and extracted with ethyl acetate (30 mL). The extract was washed withbrine, dried (Na₂SO₄), and concentrated. The product was purified byhplc to provide3-amino-N-methyl-6-[3-(4-phenyl-1H-imidazol-2-yl)phenyl]pyrazine-2-carboxamide(58 mg): ¹H NMR (400 MHz; DMSO-d₆): 8.94 (s, 1H); 8.82 (m, 1H); 8.62 (s,1H); 8.2 (d, 1H); 8.04 (d, 1H); 7.9-7.78 (m, 3H); 7.58 (t, 1H); 7.38 (m,2H); 7.24 (t, 1H); 2.82 (d, 3H); MS (EI) for C₂₁H₁₈N₆O: 371 (MH⁺).

Example 303-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide

3-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide:To a stirred solution of3-amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide (50 mg, 0.19mmol) and 4-propylbenzylamine (35.7 mg, 0.24 mmol) in TBF (5 mL) wasadded sodium cyanoborohydride (ca. 5 eq.) and the solution was stirreduntil refluxed for 1 h. The solvent was removed under reduced pressure.The residue was partitioned between ethyl acetate (50 mL) and saturatedaqueous solution of Na₂CO₃ (10 mL). The phases were separated. Theorganic layer was washed with saturated aqueous sodium chloride thendried (Na2SO₄). Filtration and concentration followed by HPLCpurification gave (24 mg, 32% yield) of3-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 9.7 (br s, 1H); 9.0 (m, 1H); 8.87 (s, 1H);8.5 (s, 1H); 8.4 (d, 1H); 7.5 (m, 6H); 7.43 (m, 2H); 4.2 (d, 2H); 2.82(d, 3H); 2.56 (m, 2H); 1.6 (m, 2H); 0.9 (m, 3H); MS (EI) for C₂₃H₂₇N₅O:390 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino]methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MH; DMSO-d₆): 9.8 (br s, 1H); 9.0 (m, 1H); 8.88 (s, 1H);8.62 (s, 1H); 8.21 (m, 1H); 8.01 (m, 3H); 7.68 (m, 1H); 7.5 (m, 2H); 7.3(t, 1H); 4.2 (d, 2H); 2.85 (t, 3H); MS (EI) for C₂₀H₁₉N₅OFBr: 446 (MH⁺).

Example 31

Scheme 13 depicts a general synthetic route for compounds of theinvention having substituents —W—X—Y according to formula I, wherein,for example, W is phenylene, X is —C(═O)NHCH₂—, and Y is an indanylgroup. As depicted, intermediate (lx), is incorporated into (lxvii), acompound of the invention.1-Amino-2,3-dihydro-R1,R2-substituted-1H-indene(s) were obtained fromcommercial sources or were prepared from cinnamic acids (or arylpropionic acids) by methods known to those skilled in the art asdepicted in Scheme 13. Cinnamic acids (lx) were hydrogenated to affordacids (lxi). Acids (lxi) were converted to the corresponding acylchlorides and subjected to electrophilic aromatic substitutionconditions to afford ketones (lxiii). Ketones (lxiii) were reduced tothe corresponding alcohols (lxiv), and the alcohols subsequentlyconverted to the corresponding azides (lxv). Azides (lxv) were reducedto form the corresponding 1-aminoindanes (lxvi). Note, azides (lxv) withchloro- or bromo-substitution on phenyl ring portion were reduced to the1-aminoindanes (lxvi) using SnCl₂ in ethyl acetate, typically.Aminoindanes (lxvi) were incorporated into compounds of the invention,e.g. (lxvii), via reductive amination, for example, as depicted. Asmentioned, amines were also incorporated via coupling with correspondingbenzyl bromides to give, for example, compounds (lxvii).

3-amino-6-(3-{[(4,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:To a stirred solution of3-amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide (50 mg, 0.19mmol) and 1-amino-4,7-difluoroindane (67.6 mg, 0.4 mmol) in THF (5 mL)was added sodium cyanoborohydride (62.8 mg, 1 mmol) and 1 drop of aceticacid. The solution was stirred overnight and solvent was removed underreduced pressure. The residue was partitioned between ethyl acetate (50mL) and saturated aqueous solution of Na₂CO₃ (10 mL). The phases wereseparated. The organic layer was washed with HCl (5 mL 0.5 M) thensaturated aqueous sodium chloride and dried (Na₂SO₄). Filtration andconcentration follow by hplc purification gave (42.2 mg, 50% yield) of3-amino-6-(3-{[(4,7-difluoro-3-methyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide.An excess of HCl in dioxane (0.2 mL, 4.0 M) was added to the solutionand the solvent was removed to give hydrochloride: ¹H NMR (400 MHz;DMSO-d₆): 10.1 (br s, 1H); 9.7 (br s, 1H); 9.0 (m, 1H); 8.85 (s, 1H);8.2 (m, 1H); 7.5 (m, 2H); 7.3-7.2 (m, 2H); 5.0 (m, 1H); 4.6-4.15 (m,3H); 3.4 (m, 1H); 2.95 (m, 1H); 2.85 (d, 3H); 2.6 (m, 1H); 2.46 (m, 1H);MS (EI) for C₂₂H₂₁N₅₀F₂ HCl: 410 (MH⁺).

3-amino-6-(3-{[(4,7-difluoro-3-methyl-2,3-dihydro-1H-inden-1-yl)amino]methyl)phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d6) 9.0 (m, NH); 8.88 (s, 1H); 8.6 (s, 1H); 8.2(s, 1H); 7.5 (m, 2H); 7.4 (m, 2H); 4.5 (m, 1H); 4.2 (m, 2H); 2.85 (m,3H); 2.8 (m, 1H); 2.2 (m, 2H); 1.3 (m, 3H); MS (EI) for C₂₃H₂₃N₅OF₂ HCl:424 (MH⁺).

3-amino-6-(3-{[(6-bromo4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.8 (s, 1H); 7.78 (m, 1H); 8.08 (s, 1H); 8.22(m, 1H); 7.4-7.3 (m, 4H); 4.2 (m, 1H); 3.8 (m, 2H); 2.9 (m, 1H); 2.83(d, 3H); 2.7 (m, 3H); 2.37 (m, 1H); 2.4 (m, 1H); MS (EI) forC₂₂H₂₁N₅OFBr: 470 (MH⁺).

3-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 9.8 (br s, NM; 9.6 (br s, NH); 8.98 (m, 1H);8.88 (s, 1H); 8.6 (s, 1H); 8.2 (m, 1H); 7.7-7.2 (m, 6H); 5.1-4.38 (m,1H); 4.38 (m, 2H); 3.4 (m, 1H); 2.95 (m, 1H); 2.85 (d, 3H); 2.43-2.6 (m,1H); MS (EI) for C₂₂H₂₂N₅OF HCl: 392 (MH⁺).

3-amino-6-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl)phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MH; CDCl₃): 9.1 (m, 1H); 8.8 (s, 1H); 8.6 (m, 1H); 8.4 (d,1H); 8.74 (d, 1H); 7.5-7.2 (m, 3H); 4.6 (m, 1H); 3.9 (m, 2H); 3.4 (m,1H); 3.0 (d, 3H); 2.9 (m, 1H); 2.5 (m, 1H); 1.3 (m, 1H); MS (EI) forC₂₂H₂₁N₅OF₂: 410 (MH⁺).

3-amino-6-(3-{[(6-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide;1H NMR (400 MHz; CDCl₃): 8.6 (s, 1H); 8.0 (br s, 1H); 7.8 (s, 1H); 7.75(m, 1H); 7.74 (m, 1H); 7.18-6.9 (m, 3H); 4.3 (m, 1H); 4.40 (m, 2H); 3.04(d, 3H); 3.0 (m, 1H); 2.56 (m, 1H); 1.85 (m, 1H); MS (EI) forC₂₂H₂₂N₅OFL 392 (MH⁺).

3-amino-6-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.6 (s, 1H); 8.0 (br s, 1H); 7.84 (s, 1H);7.8 (d, 1H); 7.4 (m, 2H); 7.5 (m, 1H); 7.0 (m, 1H); 4.25 (t, 1H); 3.92(m, 21); 3.08 (d, 3H); 3.0 (m, 1H); 2.8 (m, 1H); 2.5 (m, 1H); 1.9 (m,1H); MS (EI) for C₂₂H₂₁N₅OF₂: 410 (MH⁺).

3-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 M ; CDCl₃): 8.64 (s, 1H); 8.4 (m, 1H); 7.88 (s, 1H); 7.76(d, 1H); 7.4 (m, 2H); 6.78 (d, 1H); 6.64 (t, 1H); 4.6 (m, 1H); 3.9 (m,2H); 3.2 (m, 1H); 3.1 (d, 3H); 2.85 (m, 1H:); 2.4 (m, 1H); 2.1 (m, 1H);MS (EI) for C₂₂H₂₁N₅OF₂: 410 (MH⁺).

3-amino-6-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl]phenyl)-N-methylpyrazine-2-carboxamide: 1HNMR (400 MHz; DMSO-d₆): 8.81 (s, 1H); 8.78 (br s, 1H); 8.1 (m, 1H); 8.05(m, 1H); 7.4 (m, 3H); 7.02 (t, 1H); 4.2 (m, 1H); 3.9 (m, 2H); 3.4 (m,1H); 2.85 (d, 3H); 2.76 (m, 1H); 2.4 (m, 1H); 1.8 (m, 1H); MS (EI) forC₂₂H₂₁N₅OFBr: 472 (MH⁺).

3-amino-6-(3-{[(6-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.84 (s, 1H); 8.80 (m, 1H); 8.17 (s, 1H);8.08 (d, 1H); 7.4 (m, 4H); 7.25 (m, 2H); 4.25 (m, 1H); 3.87 (m, 2H); 2.9(m, 1H); 2.85 (d, 3H); 2.7 (m, 1H); 2.4 (m, 1H); 1.8 (m, 1H); MS (EI)for C₂₂H₂₂N₅OCl: 408 (MH⁺).

3-amino-6-(3-{[(4,6-dichloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.84 (s, 1H); 8.8 (m, 1H); 8.1 (s, 1H); 8.06(d, 1H); 7.39 (m, 4H); 4.2 (m, 1H); 3.87 (m, 2H); 2.9 (m, 1H); 2.85 (d,3H); 2.77 (m, 1H); 2.4 (m, 1H); 1.8 (m, 1H1); MS (EI) for C₂₂H₂₁N₅OCl₂:442(MH⁺).

3-amino-6-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 8.84 (s, 1H); 8.80 (m, 1H); 8.2 (s, 1H); 8.05(d, 1H); 7.4-7.23 (m, 4H); 4.25 (m, 1H); 3.87 (m, 2H); 2.95 (m, 1H);2.85 (d, 3H); 2.78 (m, 1H); 2.4 (m, 1H); 1.84 (m, 1H); MS (EI) forC₂₂H₂₂N₅OCl: 408 (MH⁺).

3-amino-6-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide: ¹H NMR (400 MHz;DMSO-d₆): 9.9 (m, 2H); 9.05 (m, 1H); 8.9 (s, 1H); 8.7 (s, 1H); 8.2 (d,1H); 8.15 (s, 1H); 7.5 (m, 3H); 7.3 (d, 1H); 4.85 (m, 1H); 4.25 (m, 2H);3.18 (m, 1H); 2.86 (m, 1H); 2.81 (d, 3H); 2.65 (m, 1H); 2.4 (m, 1H); MS(EI) for C₂₂H₂₂N₅OBr HCl: 452 (MH⁺).

3-amino-6-(3-{[(7-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₂H₂₂N₅OFHCl: 392 (MH⁺).

3-amino-N-methyl-6-(3-{[(2R)-1,2,3,4-tetrahydronaphthalen-2-ylamino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.82 (s, 1H), 8.77 (dd, 1H), 8.08 (s, 1H),8.02 (m, 1H), 7.62 (bs, 2H), 7.38 (m, 2H), 7.03 (s, 4H), 3.85 (s, 2H),3.26 (m, 2H), 3.00 (dd, 1H), 2.86 (d, 3H), 2.81 (t, 1H), 2.68 (m, 1H),2.56 (m, 1H), 2.02 (m, 1H), 1.56 (m, 1H); MS (EI) for C₂₃H₂₅N₅O: 388.4(MH⁺).

3-amino-N-methyl-6-(3-{[(2S)-1,2,3,4tetrahydronaphthalen-2-ylamino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, 46-DMSO): 8.82 (s, 1H), 8.77 (dd, 1H), 8.11 (s, 1H),8.04 (m, 1H), 7.62 (bs, 2H), 7.39 (m, 2H), 7.02 (s, 4H), 3.86 (s, 2H),3.25 (m, 2H), 3.00 (dd, 1H), 2.88 (d, 3H), 2.81 (t, 1H), 2.72 (m, 1H),2.62 (m, 1H), 2.04 (m, 1H), 1.58 (m, 1H); MS (EI) for C₂₃H₂₅N₅O: 388.4(MH⁺).

Example 32

Scheme 14 shows, analogously to Scheme 13 above, that 2-aminoindan-1-olswere also prepared for incorporation into compounds of the invention.Ketones (lxiii) were converted to azides (lxviii), followed by reductionto 2-aminoindan-1-ols (lxix). These amino alcohols were used to makecompounds of the invention, for example compounds (lxx), as depictedbelow.

3-amino-6-(3-{[(4-fluoro-1-hydroxy-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide

A solution of 4-fluoro-2,3-dihydro-1H-inden-1-one (1.29 g, 9.34 mmol)and HNIB (5.02 g, 12.1 mmol) in CH₃CN (190.0 mL) was refluxed for 1.5 h,until the solution was clear yellow. Upon cooling to r.t., NaN₃ (1.21 g,18.7 mmol) was added and the solution was stirred at r.t. for 12 h.Additional NaN₃ (0.50 g, 7.7 mmol) was added and the solution stirredfurther at r.t. for 4 h. The reaction mixture was concentrated in vacuo,and the residue was taken up in CH₂Cl₂ (100 mL). This solution waswashed with H₂O (75 mL), dried (Na₂SO₄), filtered and concentrated invacuo. The residue was purified via column chromatography (SiO₂, 5:1hexanes/EtOAc) to give 1.61 g (96% yield) of2-azido-4-fluoro-2,3-dihydro-1H-inden-1-one: ¹H NMR (400 MHz, CDCl₃):7.59 (d, 1H), 7.41 (m, 1H), 7.32 (t, 1H), 4.15 (dd, 1H), 3.55 (dd, 1H),2.89 (dd, 1H).

To a solution of 2-azido-4-fluoro-2,3-dihydro-1H-inden-1-one (0.81 g,4.5 mmol) in MeOH (15.0 mL), was added NaBH₄ (0.19 g, 4.5 mmol) in oneportion. After stirring for 10 min at r.t., the solution wasconcentrated in vacuo. The residue was taken up in EtOAc (100 mL), andthis solution was washed with saturated NaHCO₃ (aq) (50 mL), dried(Na₂SO₄), filtered and concentrated in vacuo to give 0.64 g (73% yield)of 2-azido-4-fluoro-2,3-dihydro-1H-inden-1-ol as a white solid, whichwas used without further purification: ¹H NMR (400 MHz, CDCl₃): 7.23 (m,2H), 6.97 (t, 1H), 5.15 (dd, 1H), 4.37 (q, 1H), 3.17 (d, 1H), 2.40 (d,1H).

A solution of 10% Pd/Carbon (0.070 g, 0.50 mmol)), in EtOAc (7.0 mL) wasstirred under a H₂ (g) balloon for 2 h, after which time a solution of2-azido-4-fluoro-2,3-dihydro-1H-inden-1-ol (0.98 g, 5.1 mmol) and Boc₂O(1.3 g, 6.1 mmol) in EtOAc (3.0 mL) was added. The mixture was stirredunder a H₂ (g) balloon at r.t. for 12 h. Filtration throughcelite/fritted glass funnel and concentration in vacuo gave a cruderesidue, which was purified via column chromatography (SiO₂, 3:1hexanes/EtOAc) to give 0.62 g (46% yield) of 1,1-dimethylethyl(4-fluoro-1-hydroxy-2,3-dihydro-1H-inden-2-yl)carbamate: ¹H NMR (400MHz, CDCl₃): 7.18 (m, 2H), 6.94 (nm, 1H), 5.21 (bs, 0.5H), 5.03 (bs,0.5H), 4.37 (bs, 0.5H), 4.10 (q, 0.5H), 3.24-3.40 (m, 1H), 2.59-2.86 (m,1H), 1.44 (s, 9H).

To a solution of 1,1-dimethylethyl(4-fluoro-1-hydroxy-2,3-dihydro-1H-inden-2-yl)carbamate (0.30 g, 1.1mmol) in CH₂Cl₂ (10 mL) was added TFA (1 mL), and the solution washeated to reflux. The solution was immediately cooled and concentratedin vacuo. The residue was taken up in MeOH and treated with Bio-Rad AG1-X8 resin (hydroxide form) until pH 8. The product was filtered andconcentrated in vacuo to give 0.12 g (64% yield) of2-amino-4-fluoro-2,3-dihydro-1H-inden-1-ol, which was used withoutfurther purification for the subsequent reductive amination.

A solution of 3-amino-6-(3-forylphenyl)-N-methylpyrazine-2-carboxamide(0.15 g, 0.62 mmol), 2-amino-4-fluoro-2,3-dihydro-1H-inden-1-ol (0.12 g,0.74 mmol), glacial AcOH (0.070 mL, 1.2 mmol) and NaBH(OAc)₃ (0.39 g,1.8 mmol) in THF (2.5 mmol) was heated to 70° C. for 1 h. Upon cooling,saturated NaHCO₃ (aq) was added (25 mL). The aqueous layer was extractedwith EtOAc (2×25 nm). The combined organic layers were dried (Na₂SO₄),filtered and concentrated in vacuo. The crude mixture was purified viaHPLC (reverse-phase, CH₃CN/H₂O with 0.1% TFA). Upon removal ofCH₃CN/H₂O, the product was taken up in MeOH and treated with Bio-Rad AG1-X8 resin (hydroxide form) until pH 8. The product was filtered andconcentrated in vacuo, to provide 14.1 mg (6% yield) of3-amino-6-(3-{[(4-fluoro-1-hydroxy-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d₆-DMSO): 8.81 (d, 1H), 8.77 (bs, 1H), 8.08 (d, 1H),8.02 (d, 1H), 7.38 (m, 2H), 7.22 (m, 1H), 7.16 (d, 1H), 7.10 (d, 1H),7.00 (q, 1H), 5.60 (d, 0.5H), 5.34 (bs, 0.5H), 4.91 (d, 0.5H), 4.84 (t,0.5H), 3.84-4.02 (m, 2H), 3.18 (m, 1H), 2.98 (dd, 0.5H), 2.85 (d, 3H),2.76 (dd, 0.5H), 2.52 (m, 2H); MS (EI) for C₂₂H₂₂N₅O₂F: 408 (MH⁺).

Using the analogous synthetic techniques beginning from(4-fluoro-2,3-dihydro-1H-inden-2-yl)amine [Haadsma-svensson, S. R. etal. WO 9 504 713, 1995], the following compound of the invention wasprepared:

3-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:1H NMR (400 Mz, d₆-DMSO): 8.81 (s, 1H), 8.75 (m, 1H), 8.06 (s, 1H), 8.02(m, 1H), 7.37 (m, 2H), 7.14 (m, 1H), 7.02 (d, 1H), 6.91 (t, 1H), 3.83(s, 2H), 3.60 (m, 1E), 3.11 (dd, 2H), 2.85 (d, 2H), 2.73-2.81 (m, 3H);MS (EI) for C₂₂H₂₂N₅O F: 392 (MH⁺).

Example 33

3-amino-N-methyl-6-{3-[(naphthalen-2-ylamino)methyl]phenyl}pyrazine-2-carboxamide.A solution of 3-amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide(0.075 g, 0.29 mmol), naphthalen-2-amine (0.21 g, 1.5 mmol), glacialAcOH (0.033 mL, 0.56 mmol) and NaBH(OAc)₃ (0.093 g, 0.44 mmol) in THF(1.1 mL) was heated to 80° C. for 12 h. Upon cooling, saturated NaHCO₃(aq) was added (25 mL). The aqueous layer was extracted with EtOAc (2 x25 mL). The combined organic layers were dried (Na₂SO₄), filtered andconcentrated in vacuo. The crude mixture was purified via HPLC(reverse-phase, CH₃CN/H₂O with 0.1% TFA). Upon removal of CH₃CN/H₂O, theproduct was taken up in MeOH and treated with Bio-Rad AG 1-X8 resin(hydroxide form) until pH 8. The product was filtered and concentratedin vacuo, to provide 29.1 mg (26% yield) of3-amino-N-methyl-6-{3-[(naphthalen-2-ylamino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, 4-DMSO): 8.84 (s, 1H), 8.77 (d, 1H), 8.22 (s, 1H), 8.05(dt, 1H), 7.62 (t, 2H), 7.51 (d, 1H), 7.41 (d, 2H), 7.27 (dt, 1H), 7.10(dt, 2H), 6.77 (d, 1H), 6.57 (t, 1H), 4.46 (d, 2H), 2.85 (d, 3H); MS(EI) for C₂₃H₂₁N₅O: 384 (MH⁺)

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-N-methyl-6-{3-[(naphthalen-1-ylamino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.78 (s, 1H), 8.70 (m, 1H), 8.25 (m, 1H),8.20 (s, 1H), 7.99 (m, 2H), 7.73 (m, 1H), 7.42 (m, 2H), 7.36 (m, 2H),7.16 (t, 1H), 7.05 (d, 1H), 6.96 (t, 1H), 6.42 (d, 1H), 4.57 (d, 2H),2.84 (d, 3H); MS (EI) for C₂₃H₂₁N₅O: 384 (MH⁺).

Example 343-amino-6-[3-({[(3-fluorobiphenyl-4-yl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide

A solution of 4-bromo-2-fluorobenzaldehyde (0.15 g, 0.74 mmol),tributyl(phenyl)stannane (0.27 mL, 0.81 mmol) and Pd(PPh₃)₄ (0.043 g,0.037 mmol) in PhCH₃ (2.5 mL) was heated in a sealed reaction tube to110° C. for 12 h. Additional tributyl(phenyl)stannane (0.20 mL, 0.61mmol) and Pd(PPh₃)₄ (0.043 g, 0.037 mmol) were added and the solutionwas further heated to 110° C. for 2 h. The solvent was removed in vacuo.The residue was purified via column chromatography (SiO₂, 5:1hexanes/EtOAc) to provide 0.23 g (>100% yield) of3-fluorobiphenyl-4-carbaldehyde, which was used without furtherpurification: MS (EI) for C₁₃H₉OF: 201 (MH⁺).

A solution of 3-fluorobiphenyl-4-carbaldehyde (0.030 g, 0.15 mmol),3-amino-6-[3-(aminomethyl)phenyl]-N-methylpyrazine-2-carboxamide (0.038g, 0.15 mmol), glacial AcOH (0.010 mmol, 0.15 mmol) and NaBH(OAc)₃(0.047 g, 0.22 mmol) in THF (0.6 mL) was stirred at r.t. for 12 h.Saturated NaHCO₃ (aq) was added (25 mL) and the aqueous layer wasextracted with EtOAc (2×25 mL). The combined organic layers were dried(Na₂SO₄), filtered and concentrated in vacuo. The crude mixture waspurified via HPLC (reverse-phase, CH₃CN/H₂O with 0.1% TFA). Upon removalof CH₃CN/H₂O, the product was taken up in MeOH and treated with Bio-RadAG 1-X8 resin (hydroxide form) until pH 8. The product was filtered andconcentrated in vacuo, to provide 13.4 mg (20% yield) of3-amino-6-[3-({[(3-fluorobiphenyl4-yl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.84 (s, 1H), 8.79 (d, 1H), 8.09 (bs, 1H),8.05 (m, 1H), 7.70 (m, 2H), 7.61 (t, 1H), 7.36-7.53 (m, 8H), 3.80 (d,4H), 2.86 (d, 3H); MS (EI) for C₂₆H₂₄N₅OF: 442 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-{3-[({[2-fluoro-4-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 8.83 (s, 1H), 8.79 (m, 1H), 8.07 (bs, 1H),8.05 (m, 1H), 7.58 (m, 2H), 7.54 (d, 1H), 7.37-7.50 (m, 4H), 7.15 (m,1H), 3.78 (d, 4H), 3.17 (d, 1H), 2.86 (d, 3H); MS (EI) for C₂₄H₂₂N₅OFS:448

3-amino-6-[3-({[(2-fluoro-4-furan-2-ylphenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 M , d₆-DMSO): 8.81 (s, 1H), 8.77 (m, 1H), 8.06 (bs, 1H),8.02 (m, 1H), 7.74 (d, 1H), 7.35-7.57 (m, 4H), 700 (d, 1H), 6.59 (m,1H), 3.75 (d, 4H), 2.84 (d, 3H); MS (EI) for C₂₄H₂₂N₅O₂F: 432 (MH⁺).

3-amino-6-{3-[({[2-fluoro-5-(2-thienyl)phenyl]methyl}amino)methyl]phenyl]-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d₆-DMSO): 8.80 (s, 1H), 8.75 (m, 1H), 8.07 (bs, 1H),8.02 (m, 1H), 7.77 (dd, 1H), 7.55 (m, 1H), 7.50 (dd, 1H), 7.37-7.44 (m,3H), 7.18 (dd, 1H), 7.10 (dd, 1H), 3.80 (d, 4H), 3.16 (d, 1H), 2.83 (d,3H); MS (EI) for C₂₄H₂₂N₅OFS: 448 (MH⁺).

3-amino-6-[3-({[(4-ethenyl-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d₆-DMSO): 8.80 (s, 1H), 8.75 (m, 1H), 8.04 (bs, 1H),8.01 (m, 1H), 7.25-7.48 (m, 5H), 6.69 (dd, 1H), 5.86 (d, 1H), 5.27 (d,1H), 3.75 (d, 4H), 3.16 (d, 1H), 2.85 (d, 3H); MS (EI) for C₂₂H₂₂N₅OF:392 (MH⁺).

Example 352-amino-5-[3-hydroxymethyl)phenyl]-N-methylpyridine-3-carboxamide

2-Amino-5-bromopyridine-3-carboxylic acid was prepared by bromination,para- to the 2-amino group of commercially available 2-aminonicotinicacid as described in U.S. Pat. Nos. 3,950,160 and 4,361,700.

Methyl 2-amino-5-bromopyridine-3-carboxylate: A slurry of2-amino-5-bromopyridine-3-carboxylic acid (7 g, 32.2 mmol) in methanol(150 mL) and H₂SO₄ (7 mmol) was heated to reflux for 48 h. The reactionmixture was concentrated to ca. 40 mL. Water (100 mmol) was added to theresidual oil, and the mixture neutralized with sodium carbonate. Ethylacetate (400 mL) was added and the organic layer was washed withsaturated aqueous sodium chloride then dried (Na₂SO₄) and concentratedto give the title compound (5.5 g, 73.9% yield).

2-Amino-5-bromopyridine-N-methylpyridine-3-carboxamide: A slurry of theabove methyl 2-amino-5-bromopyridine-3-carboxylate (3.0 g, 13 mmol) inmethanol was cooled to 0° C., and methylamine gas was passed through thesolution at a moderate rate for 5 min. The mixture was stirred in sealedtube at 50 ° C. for 24 h, and the methanol was removed in vacuo toprovide 2-amino-5-bromopyridine-N-methylpyridine-3-carboxamide as awhite solid (2.5 g, 80.6% yield): ¹H NMR (400 MHz; DMSO-d₆): 8.54 (br s,1H); 8.19 (d, 1H); 8.08 (d, 1H); 7.25 (s, 1H); 2.72 (d, 3H).

2-Amino-5-[3-hydroxymethyl)phenyl]-N-methylpyridine-3-carboxamide: To asolution of 2-amino-5-bromopyridine-N-methylpyridine-3-carboxamide (0.15g, 0.66 mmol) in DMF (10 mL) was added 3-hydroxymethymphenyl boronicacid (129 mg, 0.85 mmol), Pd(dppf)₂Cl₂ (10 mol % yield) and sodiumcarbonate (0.3 g) and this mixture was stirred under a nitrogenatmosphere for 5 minutes. The mixture was heated at 85° C. for 4 h. Thereaction mixture was cooled to room temperature. The mixture wasextracted with ethyl acetate (3×10 mL) and the combined organicfractions were sequentially washed with aqueous ammonium chloride (2×5mmol) and brine (2×5 mmol), dried over anhydrous sodium sulfate,filtered and evaporated in vacuo. The residue was triturated withdiethyl ether/hexanes (2:1) and the solid was collected by vacuumfiltration. Purification by column chromatography afforded a white solid(100 mg, 59% yield): ¹H NMR (400 MHz; DMSO-d₆): 8.6 (br s, NH); 8.4 (d,1H); 8.2 (d, 1H); 7.6 (s, 1H); 7.55 (d, 1H); 7.4 (t, 1H); 7.27 (d, 1H);7.2 (br s, 2NH); 5.25 (t, 1H); 4.55 (d, 2H); 2.80 (d, 3H); MS (EI) forC₁₄H₁₅N₃O: 258 (MH⁺).

Example 36

Scheme 15 depicts a general synthetic route for compounds of theinvention having substituents —W—X—Y according to formula I, wherein,for example, W is phenylene, X is —CH₂NH—, and Y is various groups.Note, as defined above any of W, X, or Y are optionally substituted;this is only a set of examples. Analogous to Scheme 10, primary amine(xlv), which in this example incorporates Y, is incorporated into acompound of the invention, (lxxiii). For example, amine (xlv), which hasY as part of its structure for example, is converted to2,4-dinitrosulfonamide (xlvi). Sulfonamide (xlvi) is used to makesulfonamide (lxxii). The transformation (xlvi) to (Ixxii) is carried outunder Mitsunobu conditions, in this case where the alcohol partner isintermediate, compound of the invention, (lxxi). As described above inrelation to Scheme 10, the sulfonamide bond is cleaved, typically butnot necessarily via addition of a primary amine e.g. n-propyl amine, tofree secondary amine (lxxiii), which in this case is a compound of theinvention.

2-Amino-5-(3-{[[(2,4-dinitrophenyl)sulfonyl][(1S)-2,3-dihydro-1H-inden-1-yl]amino}methyl}phenyl]-N-methylpyridine-3-carboxamide

N-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dinitrobenzenesulfonamide: To astirred, ice-cooled solution of 4.00 g of (S)-(+)-1-aminoindan (30.0mmol, from Sigma-Aldrich) in 113 mmol of THF was added 9.60 g (36.0mmol, 1.20 eq.) of 2,4-dinitrobenzenesulfonyl chloride, followed by 7.80mL (44.8 mmol, 1.49 eq.) of N,N-diisopropylethylamine. The ice bath wasremoved, and the mixture was stirred at room temperature for 19 h andthen concentrated. The residue was taken up in EtOAc, washed with 2×H₂O,dried over Na₂SO₄, filtered, and concentrated. The residue was sonicatedin ca. 30 mL of EtOAc until a precipitate was formed. The mixture wasdiluted to ca. 150 mL with hexanes. Filtration afforded pure product asa tan solid (8.59 g, 78.8% yield).

Triphenylphosphine (6.9 g, 26 mmol) was added to a stirred solution of2-amino-5-[3-(hydroxymethyl)phenyl]-N-methylpyridine-3-carboxamide (5.16g, 20 mmol) andN-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dinitrolbenzenesulfonamide (9.4g, 26 mmol) in benzene (150 mL). Diethyl azodicarboxylate (4.5 g, 26mmol) was then added drop wise and mixture was stirred at ambienttemperature for 4 h. Ethyl acetate (400 mL) was added and the organiclayer was washed with saturated aqueous sodium chloride then dried(Na₂SO₄). Filtration and concentration followed by column chromatography(ethyl acetate/hexane, 9:1) gave desired product (8.2 g, 50% yield).

2-amino-5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyridine-3-carboxamide:2-Amino-5-(3-{[[(2,4-dinitrophenyl)sulfonyl][(1S)-2,3-dihydro-1H-inden-1-yl]amino}methyl}phenyl]-N-methylpyridine-3-carboxamidewas treated with excess n-propylamine (4 eq) in CH₂Cl₂ (150 mL). Themixture was diluted with additional ethyl acetate (200 mL). The mixturewas subsequently washed with aqueous saturated sodium carbonate (3×30mL) and brine (3×30 mL). The combined organic fractions were dried overanhydrous sodium sulfate, filtered and concentrated in vacuo.Purification of the residue by preparative HPLC (acetonitrile/water)gave desired product (5.8 g). The compound was converted to thehydrochloride salt using 4 M solution HCl in dioxane: ¹H NMR (400 MHz;DMSO-d₆): 9.9 (br s, NH); 9.02 (s, 1H); 8.9 (s, 1H); 8.6 (s, 1H); 8.35(br s, NH); 8.2 (s, 1H); 7.8 (d, 2H); 7.75 (m, 2H); 7.37 (m, 2H1); 7.29(m, 1H); 4.85 (m, 1H); 4.25 (m, 2H); 3.4 (m, 1H); 2.9 (m, 1H); 2.80 (d,3H); 2.43 (m, 1H); 2.4 (m, 1H); MS (EI) for C₂₃H₂₄N₄O HCl: 374 (MH⁺).

2-amino-5-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide:¹H NMR (400 MH; DMSO-d₆): 9.8 (br s, 2H); 9.15 (br s, 1H); 8.8 (s, 1H);8.31 (s, 1H); 8.08 (s, 1H); 7.85 (d, 1H); 7.6 (m, 2H); 7.3 (d, 1H); 4.85(m, 1H); 4.3 (m, 2H); 3.2 (m, 1H); 2.85 (m, 1H); 2.81 (d, 3H); 2.56 (m,1H); 2.4 (m, 1H); MS (EI) for C₂₂H₂₃N₄OBr HCl: 451 (MH⁺).

2-amino-5-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 10.0 (br s, 2H); 9.18 (m, 1H); 8.8 (s, 1H);8.6 (s, 1H); 8.30 (br s, 2H); 8.25 (s, NH); 7.85-7.2 (m, 5H); 4.85 (m,1H); 4.4 (m, 2H); 3.2 (m, 1H); 2.9 (m, 1H); 2.85 (d, 3H); 2.6-2.4 (m,2H); MS (EI) for C₂₃H₂₂N₄OF₂ HCl: 409 (MH⁺).

2-amino-5-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino)methyl}phenyl)-N-methylpyridine-3-carboxamide:MS (EI) for C₂₃H₂₂N₄OFBr HCl: 469 (MH⁺).

2-amino-5-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide:¹H NMR (400 M ; DMSO-d₆): 9.4 (br s, NH); 8.9 (br s, 1H); 8.65 (br s,1H); 8.6 (s, 1H); 8.2 (s, 1H); 7.75 (m, 2H); 7.6-7.48 (m, 3H); 7.7 (d,1H); 4.85 (m, 1H); 4.3 (m, 2H); 3.8 (m, 1H); 3.18 (m, 1H); 2.85 (m, 3H);2.59-2.4 (m, 2H); MS (EI) for C₂₃H₂₃N₄OCl HCl: 407 (MH⁺).

2-amino-5-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide):¹H NMR (400 MHz; DMSO-d₆): 9.83 (br s, NH); 9.09 (br s, NH); 8.82 (s,1H); 8.58 (s, 1H); 8.22 (s, 1H); 7.99 (m, 1H); 7.8 (m, 1H); 7.67-7.44(m, 2H); 4.85 (s, 1H); 4.27 (m, 2H); 3.2 (m, 1H); 2.95 (m, 1H); MS (EI)for C₂₃H₂₂N₄OF₂: 408 (MH⁺).

2-amino-5-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide:¹H NMR (400 MHz; DMSO-d₆): 9.7 (br s, NH); 9.4 (br s, 1H); 9.0 (br s,1H); 8.7 (s, 1H); 8.57 (s, 1H); 8.1 (s, 1H); 7.8 (m, 1H); 7.5 (m, 1H);7.2 (m, 2H); 4.85 (m, 1H); 4.3 (m, 2H); 3.89 (m, 1H); 3.18 (m, 1H); 2.85(m, 3H); 2.69-2.5 (m, 2H); MS (EI) for C₂₃H₂₂N₄OF2 HCl: 409 (MH⁺).

Using a strategy that combines synthetic technique as described inrelation to both Scheme 14 and Scheme 15, the following compounds weremade:

3-Amino-6-[3-({[6-(3-hydroxypropyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:

5-Bromo-2,3-dihydro-1H-inden-1-one (1.68 g, 7.99 mmol) was dissolved inDMF and treated with triethylamine (1.61 g, 15.98 mmol), copper iodide(152 mg, 0.79 mmol) and prop-2-yn-1-ol (2.24 g, 39.96 mmol) in thepresence of Pd(PPh₃)₄ (462 mg, 0.39 mmol) at ambient temperature. Afterbeing refluxed for 16 h, the reaction mixture was extracted with ethylacetate (100 mL×3) and washed with brine. The combined organic layerswere dried over MgSO₄. Solvent removal under vacuum gave crude tan oil.Purification by preparative thin-layer chromatography afforded5-(hydroxyprop-1-yn-1-yl)-2,3-dihydro-1H-indene-1-one (1.06 g, 72%yield): ¹H NMR (400 MHz, CD₃OD): δ 7.63 (d, 1H), 7.59 (s, 1H), 7.42 (d,1H), 4.45 (s, 2H), 3.18 (m, 2H), 2.69 (m, 2H); MS (EI) for C₁₂H₁₀O₂:187.20 (MH⁺).

To a solution of 5-(hydroxyprop-1-yn-1-yl)-2,3-dihydro-1H-indene-1-one(1.06 g, 5.71 mmol) in MeOH was added 10% Pd/C and hydrogenated by meansof Pair shaker. After 12 h, the reaction mixture was filtered on Celiteand concentrated in vacuo to give5-(3-hydroxypropyl)-2,3-dihydro-1H-inden-1-one (1.03 g, 94% yield): MS(EI) for C₁₂H₁₄O₂: 191.24 (MH⁺).

5-(Hydroxyprop-1-yn-1-yl)-2,3-dihydro-1H-indene-1-one (1.03 g, 5.42mmol) was dissolved in DMF and treated withchloro-tert-butyldimethylsilane (981 mg, 6.51 mmol), imidazole (443 mg,6.51 mmol) at 0° C. The reaction mixture was allowed to reach ambienttemperature. After 10 h, the reaction mixture was extracted with ethylacetate (100 mL×3), washed with water, brine and dried over MgSO₄. Theorganic layer was concentrated under vacuum and purified by flash columnchromatography to yield the5-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-2,3-dihydro-1H-inden-1-one(1.54 g, 94% yield): ¹H NMR (400 MHz, CDCl₃): δ 7.63 (d, 1H), 7.59 (s,1H), 7.42 (d, 1H), 4.45 (t, 2H), 3.10 (m, 2H), 2.78 (m, 2H), 2.64 (m,2H), 1.82 (m, 2H), 0.95 (s, 9H), 0.06 (s, 6H).

5-(3-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}propyl)-2,3-dihydro-1H-inden-1-one(1.54 g, 5.07 mmol) was dissolved in MeOH (20 mmol) and treated withNaBH₄ (231 mg, 6.10 mmol) at 0° C. After 1 h, the reaction mixture wasquenched by slow addition of water at 0° C. The reaction mixture wasextracted with ethyl acetate (100 mmol×3), washed with water, brine anddried over MgSO4. The organic layer was concentrated under vacuum andmoved to the next reaction without further purification. To a solutionof alcohol (1.56 g, 5.079 mmol) were added DPPA (1.81 g, 6.60 mmol), DBU(1.00 g, 6.60 mmol) at 0° C. The reaction mixture was allowed to reachambient temperature and stirred for 10 h. The reaction mixture wasconcentrated in vacuo and purified by flash column chromatography togive1-[5-(3-1{[(1,1-dimethylethyl)(dimethyl)silyl]oxyl}propyl)-2,3-dihydro-1H-inden-1-yl]-2-triaz-1-en-2-yne(1.05 g, 63%, two steps): ¹H NMR (400 M, CDCl₃): δ 7.25 (d, 1H), 7.05(m, 2H), 4.79 (m, 1H), 3.59 (t, 2H), 3.00 (m, 1H), 2.78 (m, 1H), 2.63(m, 2H), 2.38 (m, 1H), 2.06 (m, 1H), 1.77 (m, 2H), 1.88 (s, 9H), 0.05(s, 6H).

1-[5-(3-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxyl}propyl)-2,3-dihydro-1H-1-yl]-2λ⁵-triaz-1-en-2-ynewas hydrogenated in MeOH on a Parr shaker (30 psi) overnight andfiltered on Celite. The organic layer was concentrated and dissolved inTHF (15 mL). To a solution of resulting amine were added3,5-dinitrobenzenesulfonyl chloride (1.02 g, 3.81 mmol),diisopropylethylamine (616 mg, 4.76 mmol) at 0° C. The reaction mixturewas allowed to reach to ambient temperature and stirred for 3 h tocomplete the reaction. The reaction mixture was concentrated in vacuoand purified by flash column chromatography to giveN-[5-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-2,3-dihydro-1H-inden-1-yl]-3,5-dinitrobenzenesulfonamide(1.16 g, 68% yield, two steps).

To a solution of3-amino-6-[3-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide, 403mg, 1.55 mmol) were addedN-[5-(3-1[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-2,3-dihydro-1H-inden-1-yl]-3,5-dinitro-benzenesulfonamide(950 mg, 1.77 mmol), triphenylphosphine (466 mg, 1.77 mmol), diethylazodicarboxylate (309 mg, 1.77 mmol) at 0 ° C. and the reaction mixturewas allowed to reach ambient temperature. After 10 h, the reactionmixture was extracted with ethyl acetate (100 mL×3), washed with water,brine and dried over MgSO₄. The organic layer was concentrated in vacuoand purified by flash column chromatography to yield3-amino-6-[3-({[5-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-2,3-dihydro-1H-inden-1-yl][(3,5-dinitrophenyl)sulfonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide(655 mg, 54% yield): ¹H NMR (400 MHz, CDCl₃): δ 8.45 (s, 1H), 8.28 (d,1H), 8.02 (m, 1H), 7.91 (m, 1H), 7.92 (d, 1H), 7.58 (m, 2H), 7.21 (m,2H), 7.06 (m, 3H), 5.74 (t, 1H), 4.45 (d, 1H), 4.27 (d, 1H), 3.61 (m,2H), 3.08 (d, 3H), 2.88 (m, 2H), 2.65 (m, 3H), 2.12 (m, 1H), 1.78 (m,2H), 0.89 (s, 9H), 0.05 (s, 6H).

3-Amino-6-[3-({[5-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-2,3-dihydro-1H-inden-1-yl][(3,5-dinitrophenyl)sulfonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide (600 mg, 0.77 mmol) was dissolved in THF andrefluxed for an hour in the presence of tetrabutylammonium fluoride inTHBF. The reaction mixture was partitioned with water and extracted withethyl acetate (10 mL×3) and dried over MgSO₄. Filteration andconcentration under vacuum gave tan oil, which was subjected to thesolution of dichloromethane and isopropylamine. After being stirred for30 min, the solvent was removed in vacuo and purified by flash columnchromatography to give the3-amino-6-[3-({[6-(3-hydroxypropyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]N-methylpyrazine-2-carboxamide(110 mg, 33% yield): ¹H NMR (400 MHz, CD₃OD): δ 8.59 (s, 1H), 8.06 (bs,1H), 7.91 (s, 1H), 7.52 (m, 1H), 7.40 (m, 2H), 7.11 (d, 1H), 7.08 (s,1H), 7.03 (d, 1H), 4.32 (d, 1H), 3.66 (t, 2H), 3.02 (d, 3H), 2.99 (m,1H), 2.81 (m, 1H), 2.69 (t, 2H), 2.44 (m, 1H), 1.90 (m, 4H), 1.32 (m,3H), 0.82 (m, 2H); MS (EI) for C₂₅H₂₉N₅O₂: 432.23 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carbonitrile:¹H NMR (400 MHz, d₆-DMSO): 8.93 (s, 1H), 7.98 (s, 1H), 7.81 (d, 1H),7.46 (br s, 2H), 7.44-7.38 (m, 3H), 7.22 (m, 1H), 7.17 (m, 2H), 4.16 (t,1H), 3.86 (m, 2H), 2.94 (m, 1H), 2.73 (m, 1H), 2.32 (m, 1H), 1.82 (m,1H); MS (EI) for C₂₁H₁₉N₅: 342.2 (MH⁺).

Example 375-(3-{[(1S)-2.3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(phenylmethyl)-4H-1,24-triazol-3-yl]pyrazin-2-amine

N-{3-[5-amino-6-(5-benzyl-4H-1,2,4-triazole-3-yl)pyrazin-2-yl]benzyl}-2,4-dinitro-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzenesulfonamide: Triphenylphosphine (47 mg, 0.17 mmol) was added to astirred solution of {3-[5-amino-6-(5-phenyl-4H-1,2,4-triazol-3-yl)pyrazine-2-yl]phenyl}methanol (50 mg, 0.14 mmol) andN-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dinitrobenzen sulfonamide (60 mg,0.16 mmol) in THF. Diethyl azodicarboxylate (31 mg, 0.17 mmol) was thenadded and mixture was stirred at ambient temperature 4 h. Ethyl acetate(20 mL) was added, and the organic layer was washed with saturatedaqueous sodium chloride, and then dried (Na₂SO₄). Filtration andconcentration followed by chromatography on silica gel afforded thetitle compound: MS (EI) for C₃₅H₂₉N₉O₆S: 704 (MH⁺).

The solution of crude benzene sulfonamide (50 mg) in dichloromethane (3mL) was treated with excess n-propylamine (4 eq). The solvent wasevaporated, and the residue chromatodraphed over silica gel withEtOAc-hexane (7:1) affording5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amineas a yellow solid (15 mg, 22% yield); ¹H NMR (400 MHz; DMSO-d₆): 8.78(s, 1H); 8.18 (s, 1H); 8.16 (d, 11H); 7.65 (br s, NH); 7.48-7.1 (m,11H)l 4.2 (m, 3H); 3.8 (m, 2H); 2.9 (m, 1H); ); 2.7 (m, 1H); 2.3 (m,1H); 1.8 (m, 1H); MS (EI) for C₂₉H₂₇N₇: 474 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4H-1,2,4-triazol-3-yl)pyrazin-2-amine:¹H NMR (400 MHz; DMSO-d₆): 9.9 (m, 1H); 8.88 (s, 1H); 8.68 (s, 1H); 8.4(br s, 1H); 8.24 (d, 1H); 7.85 (d, 1H); 7.6 (m, 2H); 7.4-7.2 (m, 3H);4.8 (m, 1H); 4.4 (m, 2H); 3.2 (m, 1H); 2.9 (m, 1H); 2.55 (m, 1H); 2.4(m, 1H); MS (EI) for C₂₂H₂₁N₇HCl: 384 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1,1-dimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine):¹H NMR (400 MHz; DMSO-d₆): 8. 8 (s, 1H); 8.6 (s, 1H); 8.4 (d, 1H); 7.8(d, 1H); 7.6-7.25 (m, 5H); 4.48 (s, 1H); 4.4 (m, 2H); 3.2 (m, 1H); 2.9(m, 1H); 2.5 (m, 1H); 2.35 (m, 1H); MS (EI) for C₂₆H₂₉N₇ HCl: 440 (MH⁺).

(1S)-N-{[3-(6-{5-[(methyloxy)methyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)phenyl]methyl3-2,3-dihydro-1H-inden-1-amine: ¹H NMR (400 M; DMSO-d₆): 8. 8 (s, 1H); 8.15 (s, 1H); 8.07 (d, 1H); 7.7 (br s, 1H);7.47(t, 1H); 7.4 (t, 1H); 7.4; (t, 1H); 5.25 (t, 1H); 4.6 (d, 2H);3.1-2.9 (m, 3H); 2.4 (m, 2H); 2.2-1.9 (m, 3H); 1.8-1.6 (m, 3H); 1.04 (t,3H); MS (EI) for C₂₀H₂₅N₇O: 380 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1-ethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine:¹H NMR (400 MHz; DMSO-d₆): 10.4 (br s, NH); 9.98 (br s, NH); 8.9 (s,1H); 8.77 (s, 1H); 8.3 (d, 1H); 7.84 (d, 1H); 7.8 (br s, 2NH); 7.5 (m,2H); 7.3 (m, 3H); 4.8 (m, 1H); 4.3 (m, 2H); 3.8-3.6(m, 3H); 3.4-2.9 (m,6H); 2.55-1.6 1 (m, 6H); 1.3 (t, 3H); MS (EI) for C₂₉H₃₄N₈ HCl: 495(MH⁺).

Example 383-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide

A solution methyl3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carboxylate (37.4 mg, 0.1mmol) in methanol (5 mL) was cooled to 0° C., and ammonia gas was passedthrough the solution at a moderate rate for 2 min. The mixture wasstirred in sealed tube at 50 ° C. for 24 h then the methanol was removedin vacuo to provide 2-amino-5-N-methylpyrazine-3-carboxamide as a solid(20 mg, 55.7% yield): ¹H NMR (400 MHz; DMSO-d₆): 8.8 (s, 1H); 8.3 (br s,1H); 8.15 (s, 1H); 8.0 (d, 1H); 7.7 (s, 1H); 7.6 (br s, 2H); 7.4 (m,3H); 7.2 (m, 3H); 4.2 (m, 1H); 3.89 (m, 2H); 2.9 (m, 1H); 2.7 (m, 1H);2.3 (m, 1H); 1.8 (m, 1H); MS (EI) for C₂₁H₂₁N₅O: 360 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2,2,2-trifluoroethyl)pyrazine-2-carboxamidewas prepared from methyl3-amino-6-[3-(hydrohymethyl)phenyl]pyrazine-2-carboxylate and2,2,2-trifluoroethylamine in a manner analogous to that described in theprevious example. ¹H NMR (400 MHz; DMSO-d₆): 9.9 (br s, 1H); 9.88 (br s,1H); 9.5 (t, 1H); 8.97 (s, 1H); 8.75 (s, 1H); 8.24 (m, 1H); 7.84 (d,1H); 7.5 (m, 2H); 7.4-7.3 (m, 3H); 4.8 (m, 1H); 4.3 (m, 2H); 4.2 (m,2H); 3.4 (m, 1H); 2.9 (m, 1H); 2.5 (m, 1H); 2.4 (m, 1H); MS (EI) forC₂₃H₂₂N₅OF₃ HCl: 422 (MH⁺).

Example 39 3-Amino-6-bromopyrazine-2-carboxamide

A suspension of methyl 3-aminopyrazine-2-carboxylate (5 g, 32.6 mmol)and 150 mL of dry methanol saturated with anhydrous ammonia were heatedin an autoclave at 110-115° C. for 24 h. Concentration and filtrationafforded 3-aminopyrazine-2-carboxamide (4.4 g, 97.7% yield) as a yellowsolid.

To a solution 3-aminopyrazine-2-carboxamide (3 g, 22 mmol) in aceticacid (25 mL) was drop wise added bromine (4.2 g, 26.5 mmol) at roomtemperature the reaction mixture was stirred for 0.5 h and Na₂CO₃ (2 eq)was added slowly. Upon added of the reaction, the solvent was removed invacuo, water (50 mL) was added to the residue and the precipitate wascollected on a filter and washed with hexane (50 mL) to give3-amino-6-bromopyrazine-2-carboxamide (4.5 g) as a yellow solid: MS (EI)for C₅H₅BrN₄O: 217 (MH⁺).

3-Amino-6-bromopyrazine-2-carbonitrile:3-Amino-6-bromopyrazine-2-carboxamide (1.5 g, 7 mmol) was dissolved inpyridine (15 mL). The solution was then cooled in an ice bath and POCl₃(2 mL) was drop wise added. The resulting mixture was stirred at roomtemperature for 2.5 h. The solvent was removed and the residue wasquenched by the careful addition of ice cooled Na₂CO₃ (5 mmol). Ethylacetate was added (45 mL) and the organic layer was separated, washedwith brine (5 mL), HCl (0.1 M aqueous solution, 1 mL) and water (5mmol), dried with K₂CO₃ and concentrated. The crude matherial wastriturated with hexane, and the resulting tan solid was filtered toprovide 0.8 g (58% yield) of the title compound: ¹H NMR (400 MHz;DMSO-d₆): 8.42 (s, 1H); 7.60 (br s, NH); MS (EI) for C₅H₃BrN₄: 199(MH⁺).

3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile: A mixture of3-amino-6-bromopyrazine-2-carbonitrile (7.7 g, 37.9 mmol),3-hydroxymetlhylphenyl boronic acid (7.4 g, 49.3 mmol), Pd(dppf)₂Cl₂ (10mol % yield), and triethylamine (16.6 mL, 113 mmol) in DMF (50 mL) wereheated at 85° C. for 12 h. The reaction was cooled to room temperatureand water (50 mL), EtOAc (100 mL) was added. The organic layer waswashed with brine (50 mL), dried (Na₂SO₄) and passed through a plug ofCelite. The solvent was removed and the residue triturated with ether(40 mL) to give a title compound (6 g) as a white solid: ¹H NMR (400MHz; DMSO-d₆): 8.9 (s, 1H); 7.9 (s, 1H); 7.8 (d, 1H); 7.5-7.3 (m, 4H);5.27 (t, 1H); 4.15 (d, 1H); MS (EI) for C_(12 H) ₁₀N₄O: 227 (MH⁺).

Example 40

Preparation of Triazoles

{3-[5-amino-6-(5-phenyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol:A mixture of 3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile(0.11 g, 0.5 mmol) and benzoic hydrazide (0.15 g, 1 mmol) were heated at180-200° C. for 30 min. After cooling, the reaction mass was taken upwith 5 mL DMF and the obtained solution was diluted with EtOAc andwater, clarified with charcoal and filtered on Celite. The organic layerwas separated. After drying over sodium sulfate, the ethyl acetate wasevaporated under reduced pressure. Purification of the residue bypreparative HPLC (Acetonitrile/water) gave desired product (50 mg): ¹HNMR (400 MHz; DMSO-d₆): 8.3 (s, 1H); 8.1 (m, 2H); 7.6-7.3 (m, 7H); 5.45(t, 1H); 4.6 (d, 2H); MS (EI) for C₂₃H₂₂N₅OF₃ HCl: 442 (MH⁺).

1-ethyl piperidine-3-carbohydrazide: Using the procedure (as describedin J. Med. Chem. (1990) 33 (1), 311-317), N-alkylation of ethylnipecotate with 1-bromoethane in ethanol gave the ethyl1-ethyl-3-piperidecarboxylate compound as a colorless liquid (85%yield). The ester (5 g, 27 mmol)) and hydrazine hydrate (5 mmol) werestirred under reflux for 4 h. Volatiles were stripped under reducedpressure. The solid was slurred in ether, filtered and dried, to give1-ethyl piperidine-3-carbohydrazide (4.5 g, 94% yield).

(3-{5-amino-6-[5-(1-ethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol was prepared from 3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile and 1-ethyl piperidine-3-carbohydrazidein a manner analogous to that described in the previous example: ¹H NMR(400 MHz; DMSO-d₆): 8.8 (s, 1H); 8.15 (s, 1H); 8.15 (s, 1H); 8.07 (d,1H); 7.7 (br s, 1H); 7.47 (t, 1H); 7.4 (t, 1H); 5.25 (t, 1H); 4.6 (d,2H); 3.1-2.9 (m, 3H); 2.4 (m, 2H); 2.2-1.9 (m, 3H); 1.8-1.6 1 (m, 3H);1.04 (t, 3H); MS (EI) for C₂₀H₂₅N₇O: 380 (MH⁺).

{3-[5-amino-6-(4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol: ¹HNMR (400 MHz; DMSO-₄): 8.8 (s, 1H); 8.4 (m, 2H); 7.7-7.3 (m, 4H); 5.2(t, 1H); 4.6 (d, 2H); MS (EI) for C₁₃H₁₂N₆O: 269 (MH⁺).

{3-[5-amino-6-(5-methyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz; DMSO-d₆+TFA): 8.8 (s, 1H); 8.1 (s, 1H); 8.05 (d, 1H);7.45 (t, 1H); 7.4 (d, 1H); 4.6 (s, 2H); 2.5 (s, 3H); MS (EI) forC₁₉H₁₆N₆O: 345 (MH⁺).

(3-{5-amino-6-[5-(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol:¹H NMR (400 MHz; DMSO-d₆): 8.8 (s, 1H); 8.1 (m, 2H); 7.6 (m, 2H);7.45-7.2 (m, 6H); 5.2 (m, 1H); 4.6 (d, 2H); 4.1 (s, 2H); MS (EI) forC₂₀H₁₈N₆O: 359 (MH⁺).

(3-{5-amino-6-[5-(1,1-dimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol:¹H NMR (400 MHz; DMSO-d₆): 8. 8 (s, 1H); 8.1 (s, 1H); 7.4 (m, 3H); 5.2(t, 1H); 4.6 (d, 2H); 1.4 (m, 9H); MS (EI) for C₁₇H₂₀N₆O: 325 (MH⁺).

{3-[5-amino-6-(5-furan-2-yl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol):MS (EI) for C₁₇H₁₄N₆O₂: 335 (MH⁺).

[3-(5-amino-6-{5-[3-(methyloxy)phenyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)phenyl]methanol):MS (EI) for C₂₀H₁₈N₆O₂: 375 (MH⁺).

Example 41

Scheme 16 depicts a general synthetic route for exemplary compounds ofthe invention according to formula I, wherein —W—X—Y is first installedand then -A-R⁷ is installed, specifically where A is a triazole. In thisexample, bromo-pyrazine (lxxiv) is coupled to boronic acid (lxxy) toafford intermediate (lxxyi). The cyano group of (lxxyi) is converted to,for example, a triazole to give (lxxyii), a compound according toformula I.

3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-ylpyrazin-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide

(3-{(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)boronic acid: Toa suspension of 3-carboxybenzene boronic acid (7 g, 42.4 mmol) in drymethylene chloride (200 mL) were added thionyl chloride (50 mL) and 3drops of DMF. The resulting mixture was stirred for 2 h at 50° C. Theclear solution was evaporated to dryness to give the crude acidchloride. To that residue were added (S)-aminoindane (5.64 g, 42.4 mmol)and triethylamine (12.8 mL, 3 eq) in THF (50 mL). The reaction mixturewas allowed to stir overnight and then poured into water (100 mL),extracted with EtOAc (3×50 mL). The combined organic extracts werewashed with brine, HCl (0.1 M, 20 mL), dried (Na₂SO₄) and concentratedto give white solid. The solid was washed with hexane to give crudetitle compound (6.2 g): MS (EI) for C₁₆H₁₆BNO₃: 282 (MH⁺).

To a mixture of (3-{(1S)-2.3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)boronic acid (6.2 g, 22.6 mmol) and3-amino-6-bromopyrazine-2-carbonitrile (4.3 g, 21.8 mmol) in DMF (40 mL)was added triethylamine (9.2 mmol) and Pd(dppf)₂Cl₂ (10 mol % yield).The deep black mixture was stirred overnight at 85° C., cooled to roomtemperature and EtOAc (200 mL) was added. The organic layer was passedthrough a plug of Celite. The pale yellow solution was washed with brine(3×20 mmol), HCl (1 M aquous solution (10 mmol), sodium carbonate (30mmol), dried (Na₂SO₄) and evaporated to dryness. The residue wasrecrystallized from hot EtOAc to give3-(5-amino-6-cyanopyrazine-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide(2.4 g, 30.9% yield): ¹H NMR (400 MHz; CD₃OD): 8.9 (m, 2H); 8.45 (s,1H); 8.15 (d, 1H); 7.92 (d, 1H); 7.65-7.38 (m, 3H); 7.22 (m, 4H); 5.6(m, 31); 3.03-2.85 (m, 2H); 2.42 (m, 1H); 2.0 (m, 1H); MS (EI) forC₂₁H₁₇N₅O: 356 (MH⁺).

A solution of3-(5-amino-6-cyanopyrazine-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide(2.4 g, 6.6 mmol) and 1,1-dimethyl(3S)-3-(hydrazinocarbonyl)piperidine-1-carboxylate (2.4 g, 10.1 mmol) inNMP (3 mL) was heated to 180-200° C. for 1 h. The solvent was removedunder reduced pressure. The residue obtained was stirred with CH₂Cl₂/TFA(20% v/v)) for 30 min., concentrated and purified by hplc. The compoundwas converted to the hydrochloride salt using a 4 M solution of HCl indioxane to afford3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz; CD₃OD): 8.65 (s, 1H); 8.6 (d, 1H); 7.6 (t, 1H); 7.7-7.8(m, 4H); 5.7 (t, 1H); 3.75-3.4 (m, 4H); 3.8-3.36 (m, 3H); 3.35-2.8 (m,3H); 2.6 (m, 1H); 2.4 (m, 2H); 2.1-2.0(m, 4H); 1.3 (t, 3H); MS (EI) forC₂₇H₂₈N₈O: 481 (MH⁺).

3-(5-amino-6-{5-[(3S)-piperidin-3-yl-4H]-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]benzamide:Using (1-R,2S)+cis-1-aminoindan-2-ol and 3-carboxybenzene boronic acid,the title compound was prepared according to the general scheme: ¹H NMR(400 MHz; CD₃OD): 8.86 (s, 1H); 8.6 (s, 1H); 8.5 (d, 1H); 8.4 (d, 1H);7.94 (d, 1H); 7.63 (m, NH); 7.6 (t, 1H); 7.25 (m, 3H);5.52 (m, 1H); 4.55(m, 1H); 3.2 (m, 4H); 2.93 (m, 4H); 2.75 (m, 1H); 2.11 (m, 11H); 1.68(m, 2H); 1.5 (m, 2H); MS (EI) for C₂₇H₂₈N₈O₂: 497 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[2-chlorophenyl)methyl]benzamide: ¹H NMR (400 MHz;DMSO-d₆): 9.3 (t, 1H); 9.0 (m, 2H); 8.8 (s, 1H); 8.73 (s, 1H); 8.45 (d,1H); 7.8 (d, 1H); 7.75 (br s, 1H, NH); 7.6 (t, 1H): 7.49 (d, 1H); 7.41(d, 1H); 7.3 (m, 2H); 4.6 (d, 2H); 3.6-2.9 (m, 4H); 2.2 (m, 1H); 1.8 (m,4H); MS (EI) for C₂₅H₂₅N₈OCl HCl: 489 (MH⁺).

3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-N-[(2-fluorophenyl)methyl]benzamide:¹H NMR (400 MHz; DMSO-d₆): 9.5 (m, 1H); 9.3-9.1 (m, 2H); 8.85 (s, 1H);8.78 (s, 1H); 8.43 (d, 1H); 7.9 (d, 1H); 7.6 (t, 1H); 7.42 (m, 4H); 4.5(d, 2H); 3.58-2.8 (m, 5H); 2.12-1.83 (m, 4H); MS (EI) for C₂₅H₂₅N₈F HCl;473 (MH⁺).

3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(3-fluorophenyl)methyl]benzamide:¹H NMR (400 MHz; DMSO-d₆): 9.4 (m, 1H); 9.0 (m, 2H); 8.9 (s, 1); 8.7 (s,1H); 8.4 (d, 1H); 7.9 (m, 1H); 7.8 (br s, NH); 7.6 (t, 1H); 7.2 (m, 2H);7.1 (m, 1H); 4.6 (d, 2H); 3.9-2.4 (m, 5H); 2.2-1.8 (m, 4H); MS (EI) forC₂₅H₂₅N₈F HCl: 473 (MH⁺).

3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3}pyrazin-2-yl)-N-[(4-fluorophenyl)methyl]benzamide:¹H NMR (400 MHz; DMSO-d₆): 9.5 (m, 1H); 9.35-9.1 (m, 2H); 8.9 (s, 1H);8.8 (s, 1H); 8.4 (d, 1H); 7.9 (d, 1H); 7.6 (t, 1H); 7.4 (m, 4H); 4.5 (d,2H); 3.6-2.9 (m, 5H); 2.2 (m, 1H); 1.8 (m, 3H); MS (EI) for C₂₅H₂₅N₈OFHCl; 473 (MH⁺).

3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(3-chlorophenyl)methyl]benzamide:¹H NMR (400 MHz; DMSO-d₆): 9.3 (t, 1H); 9.0 (m, 2H); 8.9 (s, 1H); 8.7(s, 1H); 8.4 (d, 1H); 7.9 (d, 1H); 7.6 (t, 1H); 7.4 (m, 2H); 7.2 (m,2H); 4.5 (d, 2H); 3.6-2.9 (m, 5H); 2.2 (m, 1H); 1.8 (m, 3H); MS (EI) forC₂₅H₂₅N₈OCl HCl: 489 (MH⁺).

3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(4-chlorophenyl)methyl]benzamide):¹H NMR (400 MHz; DMSO-d₆): 9.3 (t, 1H); 8.9 (m, 2H); 8.67 (s, 1H); 8.4(d, 1H); 7.8 (d, 1H); 7.7 (m, NH); 7.6 (t, 1H); 7.2 (m, 4H); 4.5 (d,2H); 3.6 (d, 1H); 3.4-3.1 (m, 3H); 3.0 (m, 1H); 2.1 (m, 1H); 1.8 (m,3H); MS (EI) for C₂₅H₂₅N₈OCl HCl: 489 (MH⁺).

Example 42 3-(Methylamino)-6-phenylpyrazine-2-carboxamide

Methyl 3-chloro-6-phenylpyrazine-2-carboxylate: To a mixture of aceticacid/hydrochloric acid (1:1, 20 mL) at 0° C. was added methyl3-amino-6-phenylpyrazine-2-carboxylate (1.02 g, 4.50 mmol). Aqueoussolution of sodium nitrite (0.77 g, 11.2 mmol) was added drop wise.During the addition, the temperature of the reaction was controlled at0-5° C. The reaction was slowly warmed to room temperature and stirredovernight. The reaction mixture was extracted with ethyl acetate (2×50mL). The organic layer was washed with water (30 mL), saturated aqueoussodium chloride (30 mL), dried over magnesium sulfate, filtered andconcentrated at reduced pressure to afford the crude methyl3-hydroxy-6-phenylpyrazine-2-carboxylate which was used in the next stepwith out any purification. The crude product was treated with phosphorusoxychloride (30 mL) and heated to 90° C. for 2 h. The reaction wascooled to room temperature and poured into ice-water mixture andextracted with ethyl acetate (3×40 mL). The organic layer was washedwith water (30 mL), saturated aqueous sodium chloride (30 mL), driedover magnesium sulfate, filtered, and concentrated to give crudeproduct. Column purification on silica (8:2 hexanes/ethyl acetate)afforded methyl 3-chloro-6-phenylpyrazine-2-carboxylate (0.22 g, 20%yield) as yellow solid: 1H NMR (400 MHz, CDCl₃): δ 8.90 (s, 1H), 8.02(t, 2H), 7.40 (t, 1H), 7.20 (br s, 2H), 3.90 (s, 3H): MS (EI) forC₁₂H₉N₂O₂Cl: 249 (MH⁺).

3-(Methylamino)-6-phenylpyrazine-2-carboxamide: To a solution of methyl3-chloro-6-phenylpyrazine-2-carboxylate (0.13 g, 0.53 mmol) intetrahydrofuran (3 mL) was added 0.65 mL of 2.0 N methylamine in THF(1.30 mmol). The reaction was heated in a sealed high-pressure test tubeto 90-95° C. overnight. The reaction was cooled to room temperature anddiluted with ethyl acetate (100 mL). The organic layer was washed 2.0 Naqueous hydrochloric acid (20 mL), saturated aqueous sodium bicarbonate(30 mL), and saturated aqueous sodium chloride (30 mL). The organiclayer was dried over magnesium sulfate, filtered and concentrated atreduced pressure to afford a yellowish product. Trituration withmethanol (2 mL) gave a solid, which was filtered and washed with etherto afford afford methyl 3-(methylamino)-6-phenylpyrazine-2-carboxylate(31 mg, 24%) as yellow solid: MS (EI) for C₁₃H₁₃N₃O₂: 244 (MH⁺). Thisintermediate ester was directly used in the next step.

A solution of of methyl 3-(methylamino)-6-phenylpyrazine-2-carboxylate(31 mg, 0.13 mmol) in methanol (5 ml) was saturated with ammonia at 0°C. The pressure tube was sealed and heated at 80-85° C. overnight. Thereaction was cooled to room temperature and the solvent removed atreduced pressure to afford crude solid product. Reverse-phase BPLCpurification gave 3-(methylamino)-6-phenylpyrazine-2-carboxamide (7 mg,25% yield) as a yellow solid: ¹H NM (400 MHz, CDCl₃): δ 8.42 (s, 1H),8.50 (br s, 1H), 7.90 (d, 3H), 7.45 (m, 2H), 7.40 (m, 1H), 3.10 (br s,3H); MS (EI) for C₁₂H₁₂N₄0: 229 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

6-phenyl-3-[(phenylmethyl)amino]pyrazine-2-carboxamide: ¹H NMR (400 MHz,CDCl₃): δ 9.01 (br t, 1H), 8.70 (s, 1H), 7.90 (m, 3H), 7.35 (m, 8H),5.60 (br s, 1H), 4.80 (d, 2H); MS (EI) for C18H₁₆N₄O: 305 (MH⁺).

6-phenyl-3-(propylamino)pyrazine-2-carboxamide: ¹H NMR (400 MHz, CDCl₃):δ 8.70 (s, 1H), 8.70 (s, 1H), 8.60 (br s, 1H), 7.44 (t, 2H), 7.40 (t,1H), 5.50 (br, s 1H), 3.50 (m, 2H), 1.70 (m, 2H), 1.02 (t, 3H); MS (EI)for C₁₄H₁₆N₄O: 257 (MH⁺).

Example 433-Amino-N-methyl-6-(5-cyclolpentyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide

3-Amino-6-bromo-N-methylpyrazine-2-carboxamide (2.0 g, 8.7 mmol) andcopper (I) cyanide (3.9 g, 43.5 mmol) were taken into DMF (20 mL) andthe mixture was heated to reflux for two hours. The mixture was allowedto cool to room temperature then diluted with ethyl acetate (250 mL).The insoluble residue was removed by filtration and the filtratepartitioned with water. The organic layer was separated and washed withwater (2×) then brine and dried over anhydrous magnesium sulfate.Filtration and concentration afforded3-amino-6-cyano-N-methylpyrazine-2-carboxamide (500 mg, 33% yield) as awhite solid: ¹H NMR (400 MHz, d₆-DMSO): 8.84 (br m, 1H), 8.67 (br s,1H), 8.65 (s, 1H), 2.77 (d, 3H).

3-Amino-6-cyano-N-methylpyrazine-2-carboxamide (839 mg, 4.7 mmol) wassuspended in ethanol (25 mL) followed by addition of 50% aqueoushydroxylamine (2 mL, 31.3 mmol) and the mixture was stirred at roomtemperature for one hour. The suspension obtained was diluted with water(2 5mL) and the insoluble solid collected by filtration and washed withwater. The solid was dried in vacuo to give3-amino-6-[(hydroxyamino)(imino)methyl]-N-methylpyrazine-2-carboxamide(664 mg, 67% yield) as a white solid: MS (EI) for C₇H₁₀N₆O₂: 211 (MH⁺).

3-Amino-6-[(hydroxyamino)(imino)methyl]-N-methylpyrazine-2-carboxamide(40 mg, 0.19 mmol) was taken into DMF (1.0 mL) followed by addition ofPL-DIPAM (diisopropylaminomethyl) resin (200 mg, 2.33 mmol/g), THF (1.0ML) and cyclopentanecarbonyl chloride (23.1 uL, 0.19 mmol). The mixturewas agitated for one hour then filtered and the resin rinsed with THF(1.0 mL). To the filtrate solution was added tetra-N-butylammoniumfluoride (TBAF) (1.0 M in THF, 20 0 uL) and the solution was allowed tostir at room temperature over 12 hours. The mixture was concentrated andthe residue partitioned with ethyl acetate and water. The organic layerwas washed with water (1×), 1.0 M aqueous hydrochloric acid (1×) thenbrine and dried over anhydrous magnesium sulfate. The material wasfiltered and concentrated then the residue purified by silica gel flashchromatography using ethyl acetate:hexanes (1:1) as eluent. The purefractions were combined, concentrated and dried in vacuo to give3-amino-N-methyl-6-(5-cyclopentyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide(23.3 mg, 43% yield) as a colorless amorphous residue: MS (EI) forC₁₃H₁₆N₆O₂: 289 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-Amino-N-methyl-6-(5-pyridin-3-yl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide:MS (EI) for C₁₃H₁₁N₇O₂: 298 (MH⁺).

3-Amino-N-methyl-6-(5-cyclohexyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide:MS (EI) for C₁₄H₁₈N₆O₂: 303 (MH⁺).

3-Amino-N-methyl-6-(5-phenyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide:MS (EI) for C₁₄H₁₂N₆O₂: 297 (MH⁺).

3-Amino-N-methyl-6-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]pyrazine-2-carboxamide:MS (EI) for C₁₅H₁₄N₆O₂: 311 (MH⁺).

3-Amino-N-methyl-6-(5-methyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide:MS (EI) for C₉H₁₀N₆O₂: 235 (MH⁺).

3-Amino-N-methyl-6-[5-(2-phenylethyl)-1,2,4-oxadiazol-3-yl]pyrazine-2-carboxamide:MS (EI) for C₁₆H₁₆N₆O₂: 325 (MH⁺).

3-Amino-N-methyl-6-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide:MS (EI) for C₁₃H₁₁N₇O₂: 298 (MH⁺).

3-Amino-N-methyl-6-[5-(1,1-dimethylethyl)-1,2,4-oxadiazol-3-yl]pyrazine-2-carboxamide:MS (EI) for C₁₂H₁₆N₆O₂: 276 (MH⁺).

3-Amino-N-methyl-6-(5-furan-2-yl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide:MS (EI) for C₁₂H₁₀N₆O₃: 286 (MH⁺).

Example 443-Amino-N-methyl-6-[3-(5-phenyl-1,2,4-oxadiazol-3-yl)phenyl]pyrazine-2-carboxamide

3-Amino-6-(3-cyanophenyl)-N-methylpyrazine-2-carboxamide (155 mg, 0.61mmol) was suspended in ethanol (2 mL) followed by addition of 50%aqueous hydroxylamine (250 uL, 4.1 mmol) and the mixture was heated toreflux for 30 minutes then allowed to cool to room temperature. Thesuspension was diluted with water (2 mL) and the solid product collectedby filtration and dried in vacuo to give crude3-amino-N-methyl-6-{3-[(hydroxyamino)(imino)methyl]phenyl}pyrazine-2-carboxamide(125 mg, 72% yield) as a yellow solid which was carried forward withoutfurther purification: MS (EI) for C₁₃H₁₅N₆O₂: 287 (MH⁺).

3-Amino-N-methyl-6-{3-[(hydroxyamino)(imino)methyl]phenyl}pyrazine-2-carboxamide(40 mg, 0.14 mmol) was suspended in DMF (750 uL) followed by addition ofPL-DIPAM (diisopropylaminomethyl) resin (100 mg, 2.33 mmol/g) andbenzoyl chloride (20 uL, 0.17 mmol). The mixture was agitated for onehour then diluted with ethyl acetate and the spent resin removed byfiltration, The organic filtrate was washed with water (3×), brine thendried over anhydrous magnesium sulfate. The mixture was then filteredand concentrated and the solid residue suspended in TIF (1 mmol)followed by addition of tetra-N-butylammonium fluoride (TBAF) (1.0 M inTHF, 100 uL) and the solution was allowed to stir at room temperatureover 12 hours. The mixture was concentrated and the residue partitionedwith ethyl acetate and water. The organic layer was washed with water(1×), 1.0 M aqueous hydrochloric acid (lx) then brine and dried overanhydrous magnesium sulfate. The material was filtered and concentratedthen the residue purified by preparative reverse phase HPLC(water/acetonitrile/0.1% TFA eluent). The pure fractions were combinedand lyophilized to afford3-amino-N-methyl-6-[3-(5-phenyl-1,2,4-oxadiazol-3-yl)phenyl]pyrazine-2-carboxamide(10.4 mg, 20% yield) as a yellow solid: MS (EI) for C₂₀H₁₇N₆O₂: 372(MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-Amino-N-methyl-6-{3-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}pyrazine-2-carboxamide:MS (EI) for C₂₁H₁₉N₆O₂: 386 (MH⁺).

3-Amino-N-methyl-6-t3-[5-(2-phenylethyl)-1,2,4-oxadiazol-3-yl]phenyl]pyrazine-2-carboxamide:MS (EI) for C₂₁H₁₉N₆O₂: 400 (MH⁺).

Example 45 3-Amino-N-methyl-6-13-[(2-phenylethyl)oxylphenyl}pyrazine-2-carboxamide

3-Amino-6-bromo-N-methylpyrazine-2-carboxamide (1.34 g, 5.8 mmol) and3-hydroxyphenylboronic acid (1.2 g, 8.7 mmol) were taken into DMF (10mL) followed by addition of[1,1′-bis(diphenylphosphinoferrocene]dichloropalladium (II)dichloromethane complex (440 mg, 0.54 mmol) and triethylamine (4.8 mL,35 mmol). The mixture was heated to 95° C. for 12 hours then cooled toroom temperature and diluted with an excess of ethyl acetate. Theorganic solution was washed with 0.5 M aqueous hydrochloric acid (1×),water (3×) then brine and dried over anhydrous magnesium sulfate. Themixture was then filtered and the organic solution concentrated and theresidue purified by silica gel flash chromatography using ethylacetate:hexanes (3:1) eluent. The pure fractions were combined andconcentrated then dried in vacuo to give3-amino-6-(3-hydroxyphenyl)-N-methylpyrazine-2-carboxamide (1.01 g, 71%yield) as a yellow solid: MS (EI) for C₁₂H₁₃N₄O₂: 245 (MH⁺).

3-Amino-6-(3-hydroxyphenyl)-N-methylpyrazine-2-carboxamide (179 mg, 0.8mmol) was taken into DMF (3 mL) followed by addition of cesium carbonate(1.3 g, 4 mmol) and 2-(bromoethyl)benzene (550 uL, 4 mmol). The mixturewas heated to 85° C. for 12 hours then allowed to cool to roomtemperature. The mixture was diluted with an excess of ethyl acetate andwashed with water (3×) then brine and dried over anhydrous magnesiumsulfate. Filtration and concentration in vacuo followed by purificationof the residue using silica gel flash chromatography using ethylacetate:hexanes (2:3) as eluent. The pure fractions were combined andconcentrated then dried in vacuo to give3-amino-N-methyl-6-{3-[(2-phenylethyl)oxy]phenyl}pyrazine-2-carboxamide(86 mg, 31% yield) as a yellow solid. ¹H NMR (400 MHz, d₆-DMSO): 8.83(s, 1H), 8.82 (br m, 1H), 7.74 (d, 1H), 7.67 (tr, 1H), 7.38-7.31 (m,6H), 7.26-7.22 (m, 1H), 6.95 (d tr, 1H), 4.31 (tr, 2H), 3.08 (tr, 2H),2.85 (d, 3H); MS (EI) for C₂₀H₂₁N₄O₂: 349 (MH⁺).

Example 463-Amino-N-methyl-6-(3-{[2-(4-methylpiperidin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide

3-Amino-6-(3-hydroxyphenyl)-N-methylpyrazine-2-carboxamide (1.01 g, 4.1mmol) was taken into DMF (10 mL) followed by addition of1,2-dibromoethane (10 mL) and cesium carbonate (2.7 g, 8.2 mmol). Themixture was warmed to 85° C. over 5 days followed by addition of anotheraliquot of cesium carbonate and 1,2-dibromoethane and heating wascontinued an additional 4 hours. The mixture was diluted with an excessof ethyl acetate and washed with water (3×) then brine and dried overanhydrous magnesium sulfate. Filtration and concentration ill vacuofollowed by purification of the residue using silica gel flashchromatography using ethyl acetate:hexanes (1:1) as eluent. The purefractions were combined and concentrated then dried in vacuo to give3-amino-6-{3-[(2-bromoethyl)oxy]phenyl)-N-methylpyrazine-2-carboxamide(486 mg, 34% yield) was a yellow solid: MS (EI) for C₁₄H₁₆N₄O₂Br: 351,353 (MH⁺).

3-Amino-6-{3-[(2-bromoethyl)oxy]phenyl}-N-methylpyrazine-2-carboxaamide(25 mg, 0.07 mmol) was taken into acetonitrile (1 mL) followed byaddition of 4-methylpiperidine (58 mg, 0.58 mmol) and the mixture wasstirred at room temperature over 12 hours. The crude reaction mixturewas purified directly by preparative reverse phase HPLC(water/acetonitrile/0.1% TFA eluent). The pure fractions were combinedand lyophilized to afford3-amino-N-methyl-6-(3-{[2-(4-methylpiperidin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide(20.2 mg, 60% yield) as an amorphous solid: MS (EI) for C₂₀H₂₈N₅O₂: 371(MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following compounds of the invention wereprepared:

3-Amino-6-[3-({2-[4-(2-hydroxyethyl)piperidin-1-yl]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₁H₃₀N₅O₃: 401 (MH⁺).

3-Amino-6-(3-{[2-(3-hydroxypyrrolidin-1-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₁₈H₂₄N₅O₃: 359 (MH⁺).

3-Amino-N-methyl-6-[3-({2-[4-(phenylmethyl)piperidin-1-yl]ethyl}oxy)phenyl]pyrazine-2-carboxamide:MS (EI) for C₂₆H₃₂N₅O₂: 447 (MH⁺).

3-Amino-N-methyl-6-{3-[(2-piperidin-1-ylethyl)oxy]phenyl}pyrazine-2-carboxamide:MS (EI) for C₁₉H₂₆N₅O₂: 357 (MH⁺).

3-Amino-6-[3-({2-[ethyl(phenylmethyl)amino]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₃H₂₈N₅O₂: 407 (MH⁺).

3-Amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₁₈H₂₆N₅O₂: 344 (MH⁺).

3-Amino-N-methyl-6-(3-{[2-(4-phenylpiperazin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide:MS (EI) for C₂₄H₃₀N₆O₂: 434 (MH⁺).

3-Amino-6-[3-({2-[methyl(phenylmethyl)amino]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₂H₂₆N₅O₂: 393 (MH⁺).

3-Amino-N-methyl-6-{3-[(2-morpholin-1-ylethyl)oxy]phenyl}pyrazine-2-carboxamide:MS (EI) for C₁₈H₂₄N₅O₃: 359 (MH⁺).

3-Amino-6-[3-({2-[(cyclopropyl)(propyl)amino]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₁H₃₀N₅O₂: 384 (MH⁺).

3-Amino-N-methyl-6-(3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide:MS (EI) for C₂₀H₂₉N₆O₂: 385 (MH⁺).

3-Amino-N-methyl-6-{3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}pyrazine-2-carboxamide:MS (EI) for C₁₈H₂₄N₅O₂: 343 (MH⁺).

3-Amino-N-methyl-6-(3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide:MS (EI) for C₁₉H₂₇N₆O₂: 371 (MH⁺).

3-Amino-6-[3-({2-[4-(2-hydroxyethyl)piperazin-1-yl]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₀H₂₉N₆O₃: 402 (MH⁺).

3-Amino-6-(3-{[2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide:MS (EI) for C₂₃H₂₆N₅O₂: 405 (MH⁺).

Ethyl4-{2-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)oxy]ethyl}piperazine-1-carboxylate:MS (EI) for C₂₁H₂₉N₆O₄: 430 (MH⁺).

Example 473-Amino-N-methyl-6-(3-{[(phenylmethyl)thiolmethyl]phenyl)pyrazine-2-carboxamide

3-Amino-6-(3-hydroxymethylphenyl)-N-methylpyrazine-2-carboxamide (130mg, 0.5 mmol) was suspended in THF (5 mL) followed by addition ofpyridine (200 uL, 2.5 mmol) and the mixture was cooled to −78° C.Thionyl chloride (100 uL, 1.4 mmol) was added by syringe and the mixturewas allowed to slowly warm to room temperature. An additional aliquot ofthionyl chloride was added at room temperature and the mixture wasallowed to stir an additional hour. The solvent was removed and theresidue partitioned with ethyl acetate and 0.1 M aqueous hydrochloricacid. The organic layer was washed with saturated aqueous sodiumbicarbonate then brine and dried over anhydrous magnesium sulfate. Themixture was filtered, concentrated and dried in vacuo to afford thecrude benzyl chloride, which was taken on without further purification.

The above chloride was taken into acetonitrile (3 mL) followed byaddition of benzyl mercaptan (100 uL, 0.86 mmol) then cesium carbonate(350 mg, 1.1 mmol) and the mixture was stirred at room temperature overone hour. The solvent was removed in vacuo and the residue partitionedwith ethyl acetate and water. The organic layer was washed with brineand dried over anhydrous magnesium sulfate. The mixture was filtered,concentrated then dried in vacuo and the residue purified by silica gelflash chromatography using ethyl acetate:hexanes (1:1) as eluent. Thepure fractions were combined, concentrated and dried in vacuo to give3-amino-N-methyl-6-(3-{[(phenylmethyl)thio]methyl}phenyl)pyrazine-2-carboxamide(77.1 mg, 40% yield) as a yellow amorphous solid: ¹H NMR (400 MHz,CDCl₃): 8.61 (s, 1H), 7.98 (br s, 1H), 7.76-7.74 (m, 2H), 7.42 (tr, 1H),7.35-7.24 (m, 8H), 3.68 (s, 2H), 3.65 (s, 2H), 3.05 (d, 3H); MS (EI) forC₂₀H₂₁N₄OS: 366 (MH⁺).

Example 483-Amino-N-methyl-6-(3-{[(phenylmethyl)sulfonyl]methyl}phenyl)pyrazine-2-carboxamide

3-Amino-N-methyl-6-(3-{[(phenylmethyl)thio]methyl}phenyl)pyrazine-2-carboxamide(73 mg, 0.2 mmol) was taken into dichloromethane (3 mL) followed byaddition of m-CPBA (99 mg, 0.4 mmol) and the mixture was stirred for 30minutes at room temperature. The solvent was removed and the residuepartitioned with ethyl acetate and saturated aqueous sodium bicarbonate.The organic layer was washed with brine and dried over anhydrousmagnesium sulfate. The mixture was filtered, concentrated and theresidue suspended in a minimum of hot methanol to give a yellow solid.The material was collected by filtration and further purified bypreparative reverse phase HPLC (water/acetonitrile/0.1% TFA eluent). Thepure fractions were combined and lyophilized to afford3-amino-N-methyl-6-(3-{[(phenylmethyl)sulfonyl]methyl}phenyl)pyrazine-2-carboxamide(35 mg, 44% yield) as a yellow solid: MS (EI) for C₂₀H₂₁N₄O₃S: 398(MH⁺).

Example 49 3-Amino-N-methyl-6-(3-{[(phenylmethyl)amino]methyl Iphenyl)pyrazine-2-carboxamide

Methyl 3-amino-6-(3-chloromethylphenyl)-N-methylpyrazine-2-carboxylate(30.6 mg, 0.11 mmol.) was taken into acetonitrile (2 mL) and THF (1 mL)followed by addition of benzylamine (12 uL, 0.11 mmol) thendiisopropylethylamine (20 uL, 0.11 mmol) and the mixture was allowed tostir at room temperature over six days. The mixture was thenconcentrated in vacuo and the residue purified by silica gel flashchromatography initially using ethyl acetate as eluent followed byelution with 10% methanol in dichloromethane. The pure fractions werecombined and concentrated then dried in vacuo to give methyl3-amino-6-(3-{[(phenylmethyl)amino]methyl}phenyl)pyrazine-2-carboxylate(4.9 mg, 13% yield) as a yellow amorphous solid: MS (EI) for C₂₀H₂₁N₄O₂:349 (MH⁺).

Methyl3-amino-6-(3-{[(phenylmethyl)amino]methyl}phenyl)pyrazine-2-carboxylate(4.9 mg, 0.014 mmol) was taken into methanol (2 mL) and the solution wassaturated with methylamine gas. The mixture was allowed to stir for twohours in a sealed vessel then concentrated and dried in vacuo to give3-amino-N-methyl-6-(3-{[(phenylmethyl)amino]methyl}phenyl)pyrazine-2-carboxamide(4.9 mg, 100% yield) as a yellow amorphous solid: MS (EI) for C₂₀H₂₂N₅0:348 (MH⁺).

Example 503-Amino-N-methyl-6-(3-{(phenylmethyl)oxylmethy}phenyl)pyrazine-2-carboxamide

Methyl 3-amino-6-(3-hydroxymethylphenyl)-N-methylpyrazine-2-carboxylate(75 mg, 0.3 mmol) was taken into THF (2 mL) followed by addition ofpyridine (120 uL, 1.5 mmol) and the solution was cooled to 0° C. Thionylchloride (42 uL, 0.6 mmol) was added to the mixture by syringe followedby warming to room temperature. The mixture was then stirred for twohours and partitioned with ethyl acetate and 1 M aqueous hydrochloricacid. The organic layer was washed with water (1x) then brine and driedover anhydrous sodium sulfate. The mixture was filtered and concentratedfollowed by silica gel flash chromatography using ethyl acetate:hexanes(1:1) as eluent. The pure fractions were combined and concentrated thendried in vacuo to give methyl3-amino-6-(3-chloromethylphenyl)-N-methylpyrazine-2-carboxylate (30 mg,37% yield) as a yellow solid: MS (EI) for C₁₃H₁₃N₃O₂Cl: 278, 280 (MH⁺).

Methyl 3-amino-6-(3-chloromethylphenyl)-N-methylpyrazine-2-carboxylate(18 mg, 0.06 mmol) and silver oxide (15 mg, 0.06 mmol) were added tobenzyl alcohol (2 mL) and the mixture was heated to 110° C. over 15hours. The benzyl alcohol was removed in vacuo and the residue purifiedby silica gel flash chromatography using ethyl acetate:hexanes (1:1) aseluent. The pure fractions were combined and concentrated then dried illvacuo to give methyl3-amino-6-(3-{[(phenylmethyl)oxy]methyl}phenyl)pyrazine-2-carboxylate(5.8 mg, 28% yield) as a yellow solid: MS (EI) for C₂₀H₂₀N₃O₃: 350(MH⁺).

Methyl3-amino-6-(3-{[(phenylmethyl)oxy]methyl}phenyl)pyrazine-2-carboxylate(5.8 mg, 0.017 mmol) was taken into methanol (2 mL) and the solution wassaturated with methylamine gas, The mixture was allowed to stir for twohours in a sealed vessel then concentrated. The residue was purified bysilica gel flash chromatography using ethyl acetate:hexanes (2:3) aseluent. The pure fractions were combined and concentrated then dried illvacuo to give3-amino-N-methyl-6-(3-{[(phenylmethyl)oxy]methyl}phenyl)pyrazine-2-carboxamide(4.1 mg, 69% yield) as a yellow amorphous solid: MS (EI) for C₂₀H₂₁N₄O₂:349 (MH⁺).

Example 51

Scheme 17 shows that bromo-aromatic compounds were dimerized in somecases to make compounds according to formula I. In this example,bromo-pyrazine (lxxviii) is dimerized using boronic ester (lxxix), forexample, to give (lxxx).

3-Amino-6-bromo-N-methylpyrazine-2-carboxamide: (50.0 mg, 0.22 mmol) wasdissolved in DMNF followed by addition of bis(pinacolate)diborane (1.57g, 0.43 mmol), KOAc (32.0 mg, 0.33 mmol) and PdCl₂(dppf) (10 mol %, 15.8mg). This mixture was stirred at 80° C. under nitrogen for 12 hours. Thereaction mixture was poured into water (10 mL), and extracted with ethylacetate (3×20 mL). The organic layers were washed with brine (50 mL)then dried over anhydrous sodium sulfate. Filtration, concentration andpurification by MPLC gave a solid that was dried to afford 8.45 mg(11.3% yield) of product: ¹H NMR (400 MHz, CDCl₃): δ 8.20 (s, 1H), 7.80(s, 1H), 7.45 (s, 1H), 3.00 (d, 6H); MS (EI) for C₁₂H₁₄N₈O₂: 303.45(MH⁺).

Example 523-Amino-6-[3-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide

3-Amino-6-bromo-N-methylpyrazine-2-carboxamide (2.00 g, 8.65 mmol) wasdissolved in DMF followed by addition of 3-hydroxymethyl phenyl boronicacid (1.57 g, 10.32 mmol), K₂CO₃ (3.0 g, 21.7 mmol) and Pd(PPh₃)₄ (10mol %, 1.0 g). This mixture was stirred at 90° C. under nitrogen for 12hours. The reaction mixture was poured into water (150 mL), andextracted with ethyl acetate (3×50 mL). The organic layers were washedwith brine (50 mL) then dried over anhydrous sodium sulfate.Filteration, concentration and column chromatography on silica (50%ethylacetate/hexanes) gave a solid which was dried to afforded 2.02 g(92% yield) of the title compound; ¹H NMR (400 MHz, d6-DMSO): δ0 8.80(s, 1H), 8.74 (br, 1H), 8.01(s, 2H), 7.45 (m, 4H), 5.21(t, 1H), 4.60 (d,2H), 2.81(d, 3H); MS (EI) for C₁₃H₁₄N₄O₂: 259.38 (MH⁺).

3-Amino-6-[3-(bromomethyl)phenyl]-N-methylpyrazine-2-carboxamide3-Amino-6-[3-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide (1.00g, 3.87 mmol) was dissolved in dichloromethane followed by addition oftriphenylphosphine (1.83 g, 6.98 mmol) and carbon tetrabromide (2.13 g,6.42 mmol). This mixture was stirred under nitrogen overnight.Concentration and column chromatography on silica (20% -50%ethylacetate/hexanes) gave a solid which was dried to afforded 0.42 g(39% yield) of intennediate 2. ¹H NMR (400 MHz, CDCl₃): δ 8.60 (s, 1H),7.45 (m, 5H), 4.60 (d, 2H), 3.05(d, 3H); MS (EI) for C₁₃H₁₃BrN₄O: 323.20(M+2).

3-Amino-6-(3-{[5-methyl-pyrazine-2-ylmethyl)-amino]-methyl}-phenyl)-pyrazine-2-carboxylicacid methylamide: Intermediate 2 (31.0 mg, 1.12 mmol) was dissolved intoacetonitrile (0.5 M solution) followed by addition of DIPEA (1.344 mmoL)and C-(5-methyl-pyrazin-2-yl)-methylanine (28.0 mg, 2.27 mmoL) and wasstirred overnight at RT. This reaction was poured into water and brinemixture and extracted with ethylacetate (3×20 mL). The combined organiclayer was dried over anhydrous sodium sulfate. Filteration,concentration and purified by MPLC and dried to give a yellow powder. ¹HNMR (400 MHz, d6-DMSO): δ 8.80 (s, 1H), 8.45 (s, 2H), 8.10 (s, 1H), 7.98(m, 1H), 7.40 (m, 1H), 7.38 (m, 1H), 3.98 (s, 2H), 3.96 (s, 2H), 3.00(s, 3H), 2.50 (s, 3H); MS (EI) for C₁₉H₂₁N₇O: 364.47 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

3-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.90 (m, 2H), 8.00 (m, 2H), 7.60 (m, 4H),7.40 (m, 8H), 3.80 (d, 4H), 2.80 (d, 3H); MS (EI) for C₂₆H₂₅NO₅: 424.21(MH⁺).

3-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.60 (s, 1H), 7.80 (m, 2H), 7.35 (m, 1H),3.75 (s, 2H), 3.65 (s, 2H), 3.30 (d, 3H); MS (EI) for C₂₆H₂₅NO₅: 424.48(MH⁺).

3-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.90 (m, 2H), 8.03 (m, 2H), 7.40 (m, 2H),6.60 (m, 3H), 5.70 (s, 1H), 4.11 (m, 2H), 3.80 (s, 2H), 3.60 (s, 2H),3.20 (s, 2H), 2.80 (d, 3H); MS (EI) for C₂₂H₂₄N₆O₂: 405.39 (MH⁺).

3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.40 (br, 2H), 8.80 (m, 2H), 8.21 (m, 2H),7.40 (m, 4H), 4.38 (d, 4H), 2.83 (d, 3H); MS (EI) for C₂₀H₁₉NO₅F₂:384.43 (MH⁺).

3-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d6-DMSO): δ 9.40 (br, 2H), 8.80 (m, 2H), 8.21 (m, 2H),7.40 (m, 4H), 4.38 (d, 4H), 2.83 (d, 3H); MS (EI) for C₂₀H₁₉NO₅F₂:384.41 (MH⁺).

3-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.05 (m, 2H), 7.35 (m, 6H),3.80 (s, 4H), 2.80 (d, 3H); MS (EI) for C₂₀H₁₉NO₅F₂; 384.41 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.05 (m, 2H), 7.80 (m, 2H),7.60 (m, 3H), 7.40 (m, 2H), 3.80 (d, 4H), 3.20 (s, 3H), 2.80 (d, 3H); MS(EI) for C₂₁H₂₃N₅O₃S: 426.42 (MH⁺).

3-amino-6-(3-{[(2,2-diphenylethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.05 (m, 2H), 7.60 (m, 2H),7.22 (m, 11H), 4.20 (m, 1H), 3.80 (s, 4H), 2.80 (d, 3H); MS (EI) forC₂₇H₂₇NO₅: 438.48 (MH⁺).

3-amino-N-methyl-6-{3-[({[3-(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (d, 2H), 8.11 (d, 2H), 7.90 (m, 2H),7.60 (m, 1H), 7.40 (m, 3H), 7.00 (m, 4H), 3.80 (d, 4H), 2.92 (d, 3H); MS(EI) for C₂₆H₂₅N₅O₂: 440.47 (MH⁺).

3-amino-6-[3-({[(4-aminophenyl)methyl]amino]methyl)phenyl]-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.11 (d, 2H), 7.40 (m, 2H),7.00 (m, 1H), 6.50 (m, 2H), 4.95(s, 2H), 3.80 (s, 2H), 3.60 (s, 2H),2.80 (d, 3H); MS (EI) for C₂₀H₂₂N₆O: 363.44 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.65 (s, 2H), 8.11 (s, 1H), 7.96 (d, 1H),7.40 (m, 5H), 6.92 (m, 6H), 3.80 (d, 4H), 2.92 (d, 3H); MS (EI) forC₂₆H₂₅N₅O₂: 440.47 (MH⁺).

3-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)methyl]pheny;}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.11 (s, 1H), 7.90 (d, 1H),7.40 (m, 1H), 7.20 (m, 2H), 6.60 (d, 2H), 3.85 (d, 4H), 3.80 (s, 6H),2.95 (d, 3H); MS (EI) for C₂₂H₂₅N₅O₃: 408.47 (MH⁺).

3-amino-6-[3-({[(2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.11 (s, 1H), 7.90 (d, 1H),7.40 (m, 6H), 3.85 (d, 4H), 2.95 (d, 3H); MS (EI) for C₂₀H₂₀N₅OF: 366.45(MH⁺).

3-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.80 (s, 2H), 8.90 (m, 2H), 8.40 (s, 1H),8.20 (s, 1H), 7.50 (m, 2H), 7.20 (m, 2H), 4.30 (d, 4H), 2.80 (d, 3H); MS(EI) for C₂₀H₁₉N₅OF₂: 384.42 (MH⁺).

3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOE): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H),7.40 (m, 3H), 6.80 (m, 4H), 4.20 (s, 4H), 3.80 (s, 2H), 3.60 (s, 2H),3.00 (d, 311); MS (EI) for C₂₂H₂₃N₅O₃: 406.49 (MH⁺).

3-amino-N-methyl-6-[3-({[(2-piperidin-1-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H),7.40 (m, 6H), 3.80 (d, 4H), 2.99 (d, 3H), 2.80 (d, 4H), 1.60 (m, 6H); MS(EI) for C₂₅H₃₀N₆O: 431.50 (MH⁺).

3-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.90 (m, 2H), 8.10 (m, 2H), 7.40 (m, 6H),3.80 (d, 4H), 2.80 (d, 3H); MS (EI) for C₂₀H₁₉N₅OCl₂: 416.29 (M⁺).

3-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.90 (m, 2H), 8.10 (m, 2H), 7.40 (m, 6H),3.80 (d, 4H), 2.80 (d, 3H); MS (EI) for C₂₀H₁₉N₅OCl₂: 416.32 (M⁺).

3-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H),7.40 (m, 2H), 7.10 (m, 4H), 3.90 (s, 2H), 3.60 (m, 1H), 3.20 (m, 2H),3.00 (s, 3H), 2.80 (m, 2H); MS (EI) for C₂₂H₂₃N₅O: 374.42 (MH⁺).

3-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylmethyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.10 (m, 2H), 7.40 (m, 2H),7.20 (m, 4H), 3.98 (s, 2H), 3.82 (s, 4H), 2.80 (d, 3H); MS (EI) forC₂₁H₂₁N₅O: 360.45 (MH⁺).

3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H),7.40 (m, 3H), 7.10 (m, 3H), 4.40 (m, 1H), 3.97 (m, 2H), 3.10 (m, 1H),3.00 (s, 3H), 2.94 (m, 1H), 2.40 (m, 1H), 2.00 (m, 1H); MS (EI) forC₂₂H₂₃N₅O: 374.45 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H),7.40 (m, 3H), 7.10 (m, 3H), 4.40 (m, 1H), 3.97 (m, 2H), 3.10 (m, 1H),3.00 (s, 3H), 2.94 (m, 1H), 2.40 (m, 1H), 2.00 (m, 1H); MS (EI) forC₂₂H₂₃N₅O: 374.46 (MH⁺).

3-amino-N-methyl-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H),7.40 (m, 1H), 7.30 (m, 1H), 7.08 (m, 2H), 4.40 (m, 1H), 3.80 (d, 4H),3.00 (s, 3H); MS (EI) for C₂₀H₁₈N_(5l OF) ₃: 402.40 (MH⁺).

3-amino-N-methyl-6-[3-({[(1R)-1-phenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.00 (s, 1H), 7.90 (d, 1H),7.40 (m, 6H), 3.80 (m, 1H), 3.60 (m, 2H), 3.00 (s, 3H), 1.40 (d, 3H); MS(EI) for C₂₁H₂₃N₅O: 362.44 (MH⁺).

3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.90 (m, 2H), 8.20 (s, 1H), 8.02 (d, 1H),7.50 (m, 4H), 7.20 (m, 3H), 4.80 (br, 1H), 4.40 (m, 1H), 4.00 (m, 3H),2.95 (m, 5H); MS (EI) for C₂₂H₂₃N₅O₂: 390.28 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.90 (s, 1H), 8.15 (s, 1H), 7.90 (d, 1H),7.60 (m, 2H), 7.40 (m, 6H), 7.10 (m, 1H), 3.80 (m, 4H), 3.00 (s, 3H); MS(EI) for C₂₄H₂₃N₅OS: 430.42 (MH³⁰).

3-amino-N-methyl-6-(3-[({[3-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.60 (s, 1H), 8.80 (m, 2H), 8.15 (m, 4H),7.40 (m, 5H), 4.00 (s, 1), 3.80 (s, 3H), 2.80 (d, 3H); MS (EI) forC₂₂H₂₁N₇OS: 432.42 (MH⁺).

3-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}methyl)phenyl]methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (m, 1H),7.40 (m, 5H), 3.80 (d,4H), 2.95 (s, 3H); MS (EI) for C₂₀H₁₉N₅OFCl:400.41 (Mh⁺).

3-amino-N-methyl-6-{3-[({[3-(trifluoromethyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.10 (s, 1H), 7.90 (m, 1H),7.40 (m, 6H), 3.80 (d, 4H), 2.95 (s, 3H); MS (EI) for C₂₁H₂₀N₅OF₃:416.44 (MH⁺).

3-amino-N-methyl-6-[3-({[(1S)-1-phenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.00 (s, 1H), 7.90 (d, 1H),7.40 (m, 6H), 3.80 (m, 1H), 3.60 (m, 2H), 3.00 (s, 3H), 1.40 (d, 3H); MS(EI) for C₂₁H₂₃N₅O: 362.49 (MH⁺).

3-amino-6-[3-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.00 (s, 1H), 7.90 (d, 1H),7.40 (m, 7H), 3.80 (m, 2H), 3.60 (m, 3H), 3.00 (s, 3H); MS (EI) forC₂₁H₂₃N₅O₂: 378.48 (MH⁺).

methyl(2S)-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)methyl]amino}(phenyl)ethanoate:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.00 (s, 1H), 7.90 (d, 1H),7.40 (m, 7H), 3.80 (m, 6H), 3.00 (s, 3H); MS (EI) for C₂₂H₂₃N₅O₃: 406.49(MH⁺).

3-amino-N-methyl-6-[3-({[1-(phenylmethyl)pyrrolidin-3-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.60 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H),7.38 (m, 9H), 3.80 (d, 2H), 3.60 (s, 2H), 3.40 (m, 1H), 2.90 (s, 3H),2.82 (m, 1H), 2.60 (m, 2H), 2.40 (m, 1H), 2.18 (m, 1H), 1.70 (m, 1H); MS(EI) for C₂₄H₂₈N₆O: 417.47 (MH⁺).

3-amino-6-(3-{[ethyl(phenylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.60 (s, 1H), 7.90 (d, 1H), 7.82 (m, 1H),7.30 (m, 8H), 3.61(d, 2H), 3.59 (d, 2H), 2.90 (s, 3H), 2.50 (q, 2H),1.10 (t, 3H); MS (EI) for C₂₂H₂₅N₅O: 376.44 (MH⁺).

3-amino-N-methyl-6-[3-({[(2S)-2-phenylcyclopropyl]amino}methyl)phenyl]pyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.60 (s, 1H), 7.99 (s, 1H), 7.85 (d, 1H),7.40 (m, 2H), 7.15 (m, 5H), 6.90 (m, 2H), 3.90 (s, 2H), 2.90 (d, 3H),2.38 (m, 1H), 1.85 (m, 1H), 1.10 (m, 1H), 1.00 (m, 1H); MS (EI) forC₂₂H₂₃N₅O: 374.43 (MH⁺).

3-amino-N-methyl-6-(3-{[(1-methyl-1-phenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz, d4-MeOH): δ 8.61 (s, 1H), 7.99(s, 1H), 7.85 (d, 1H), 7.60 (m, 2H), 7.40 (m, 7H), 3.42 (s, 2H), 3.00(s, 3H), 1.60 (s, 6H); MS (EI) for C₂₂H₂₅N₅O: 376.42 (MH^(÷)).

3-amino-6-{3-[(9H-fluoren-9-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.61 (s, 1H), 7.99 (s, 1H), 7.85 (d, 1H),7.70 (m, 5H), 7.40 (m, 7H), 7.20 (d, 1H), 3.41 (s, 2H), 3.00 (s, 3H); MS(EI) for C₂₆H₂₃N₅O: 422.39 (MH⁺).

3-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.15 (s, 1H), 7.90 (d, 1H),7.42 (m, 4H), 7.20 (m, 4H), 4.20 (m, 2H), 3.40 (s, 3H), 3.10 (m, 1H),2.95 (m, 1H); MS (EI) for C₂₂H₂₃N₅O₂: 390.25 (MH⁺).

3-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.15 (s, 1H), 7.90 (d, 1H),7.42 (m, 7H), 3.85 (s, 2H), 3.61 (m, 1H), 3.20 (m, 2H), 2.95 (s, 3H),2.80 (m, 2H); MS (EI) for C₂₂H₂₂N₅OBr: 452.10 (M+2).

3-amino-N-methyl-6-[3-({[(1S,2R)-2-(methyloxy)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.15 (s, 1H), 7.90 (d, 1H),7.42 (m, 4H), 7.20 (m, 4H), 4.20 (m, 2H), 3.40 (s, 3H), 3.40 (s, 3H),3.10 (m, 1H), 3.00 (s, 3H), 2.95 (m, 1H); MS (EI) for C₂₃H₂₅N₅O₂: 404.27(MH⁺).

3-amino-6-(3-{[(5-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.15 (s, 1H), 7.90 (d, 1H),7.42 (m, 4H), 7.10 (m, 3H), 4.40 (s, 2H), 3.40 (m, 2H), 3.10 (m, 1H),2.75 (m, 1H), 2.40 (m, 1H); MS (EI) for C₂₂H₂₂N₅OF: 392.27 (MH⁺).

3-amino-6-[3-({[(2S)-5-bromo-2,3-dihydro-1H-inden-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.15 (m, 2H), 7.35 (m, 6H),3.80 (s, 2H), 3.58 (m, 1H), 3.16 (m, 2H), 2.82 (m, 3H), 2.70 (m, 2H); MS(EI) for C₂₂H₂₂N₅OBr: 454.14 (M+2).

3-amino-N-methyl-6-[3-({[(1R,2S)-2-(methyloxy)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.15 (s, 1H), 7.90 (d, 1H),7.42 (m, 4H), 7.20 (m, 4H), 4.20 (m, 2H), 3.40 (s, 3H), 3.10 (m, 1H),3.00 (s, 3H), 2.95 (m, 1H); MS (EI) for C₂₃H₂₅N₅O₂: 404.27 (MH⁺).

3-amino-N-methyl-6-(3-{[(3-oxo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.15 (s, 1H), 7.90 (d, 1H),7.42 (m, 4H), 7.20 (m, 4H), 4.50 (m, 1H), 3.90 (s, 2H), 3.40 (m, 1H),3.02 (m, 1H), 3.00 (s, 3H), 2.60 (m, 1H); MS (EI) for C₂₂H₂₁N₅O₂: 388.19(MH⁺).

3-amino-6-[3-({[(1S)-4-fluoro-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide¹H NMR (400 MHz, d4-MeOH): δ 8.64 (s, 1H), 8.10 (s, 1H), 7.85 (d, 1H),7.40 (m, 3H), 7.20 (m, 3H), 6.90 (t, 1H), 4.40 (m, 1H), 3.90 (s, 2H),3.10 (m, 1H), 2.98 (s, 3H), 2.80 (m, 1H), 2.42 (m, 1H), 2.10 (m, 1H); MS(ED) for C₂₂H₂₁N₅OF: 392.16 (MH⁺).

3-amino-6-[3-({[(1S)-5,7-difluoro-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.64 (s, 1H), 8.10 (s, 1H), 7.85 (d, 1H),7.40 (m, 3H), 7.20 (m, 2H), 4.50 (m, 1H), 3.90 (m, 2H), 3.20 (m, 1H),3.00 (s, 3H), 2.85 (m, 1H), 2.42 (m, 1H), 2.15 (m, 1H): MS (EI) forC₂₂H₂₁N₅OF₂: 410.20 (MH⁺).

3-amino-N-methyl-6-[3-({[(1S)-5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.40 (m, 9H), 7.05 (m, 1H), 4.38 (m, 1H), 3.90 (m, 2H), 3.18 (m, 1H),3.00 (s, 3H), 2.85 (m, 1H), 2.42 (m, 1H), 2.15 (m, 1H); MS (EI) forC₂₆H₂₅N₅OS: 456.14 (MH⁺).

3-amino-6-(3-{[(4-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.40 (m, 6H), 7.16 (m, 1H), 4.42 (m, 1H), 3.90 (m, 2H), 3.15 (m, 1H),3.00 (s, 3H), 2.82 (m, 1H), 2.42 (m, 1H), 2.02 (m, 1H); MS (EI) forC₂₂H₂₂N₅OBr: 454.01 (M+2).

3-amino-N-methyl-6-(3-{[(4-phenyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.40 (m, 9H), 7.05 (m, 3H), 4.38 (m, 1H), 3.90 (m, 2H), 3.18 (m, 1H),3.00 (s, 3H), 2.85 (m, 1H), 2.42 (m, 1H), 2.15 (m, 1H); MS (EI) forC₂₈H₂₇N₅O: 450.20 (MH⁺).

3-amino-N-methyl-6-[3-({[4-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.42 (m, 7H), 7.27 (m, 2H), 7.11 (m, 1H), 4.38 (m, 1H), 3.90 (m, 2H),3.30 (m, 1H), 3.00 (m, 1H), 2.95 (s, 3H), 2.42 (m, 1H), 2.12 (m, 1H); MS(EI) for C₂₆H₂₅N₅OS: 456.15 (MH⁺).

3-amino-N-methyl-6-[3-({[(2R)-6-phenyl-1,2,3,4-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.60 (m, 2H), 7.30 (m, 10H), 4.70 (m, 1H), 4.00 (m, 2H), 3.18 (m, 1H),3.11 (m, 1H), 2.99 (s, 3H), 2.85 (m, 1H), 2.70 (m, 1H), 2.12 (m, 1H),1.70 (m, 1H); MS (EI) for C₂₉H₂₉N₅O: 464.21 (MH⁺).

3-amino-N-methyl-6-{3-[({5-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.40 (m, 5H), 6.80 (m, 2H), 4.35 (m, 1H), 4.10 (m, 2H), 3.90 (m, 2H),3.70 (m, 4H), 3.10 (m, 1H), 3.00 (s, 3H), 2.85 (m, 1H), 2.83 (m, 2H),2.60 (m, 4H), 2.40 (m, 1H), 2.05 (m, 1H); MS (EI) for C₂₈H₃₄N₆O₃: 503.17(MH⁺).

3-amino-6-{3-[({5-[(cyanomethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.40 (m, 5H), 6.90 (m, 2H), 4.95 (s, 2H), 4.35 (m, 1H), 3.90 (m, 2H),3.10 (m, 1H), 3.00 (s, 3H), 2.85 (m, 1H), 2.40 (m, 1H), 2.05 (m, 1H); MS(EI) for C₂₄H₂₄N₆O₂: 429.17 (MH⁺).

3-amino-N-methyl-6-[3-({[5-(1H-1,2,4-triazol-1-yl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 9.10 (s, 1H), 8.70 (s, 1H), 8.17 (s, 2H),7.90 (d, 1H), 7.60 (m, 4), 7.40 (m, 3H), 4.40 (m, 1H), 3.95 (m, 2H),3.16 (m, 1H), 3.00 (s, 3H), 2.92 (m, 1H), 2.50 (m, 1H), 2.03 (m, 1H); MS(EI) for C₂₄H₂₄N₈O: 441.17 (MH⁺).

3-amino-6-(3-{[(4-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:1H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.40 (m, 2H), 7.20 (m, 2H), 6.65 (m, 3H), 4.40 (br, OH, 1H), 4.21 (m,1H), 3.90 (m, 2H), 3.10 (m, 1H), 3.00 (s, 3H), 2.85 (m, 1H), 2.40 (m,1H), 2.05 (m, 1H); MS (EI) for C₂₂H₂₃N₅O₂: 390.16 (MH⁺).

3-amino-N-methyl-6-{3-[({4-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.40 (m, 4H), 7.20 (m, 1H), 7.00 (m, 1H), 6.80 (m, 1H), 4.35 (m, 1H),4.10 (m, 2H), 3.90 (m, 2H), 3.70 (m, 4H), 3.10 (m, 1H), 3.00 (s, 3H),2.85 (m, 1H), 2.83 (m, 2H), 2.60 (m, 4H), 2.40 (m, 1H), 2.05 (m, 1H); MS(EI) for C₂₈H₃₄N₆O₃: 503.20 (MH⁺).

3-amino-6-(3-{[(4-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.17 (s, 1H), 7.92 (d, 1H),7.42 (m, 4H), 7.10 (m, 1H), 6.95 (m, 1H), 6.61(m, 1H), 4.31 (m, 1H),3.90 (m, 2H), 3.10 (m, 1H), 3.00 (s, 3H), 2.76 (m, 1H), 2.40 (m, 1H),2.05 (m, 1H); MS (EI) for C₂₂H₂₃N₅O₂: 390.16 (MH⁺).

3-amino-6-[3-(1H-imidazol-1-ylmethyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.81 (s, 1H), 8.76 (m, 1H), 8.10 (m, 2H),7.80 (s, 1H), 7.66 (br s, 2H), 7.41 (t, 1H), 7.24 (s, 1H), 7.17 (d, 1H),6.89 (s, 1H), 5.24 (s, 2H), 2.86 (d, 3H); MS (EI) for C₁₆H₁₆N₆O: 309.2(MH⁺).

Example 53

Scheme 18 shows how alcohols were converted to amines to make compoundsaccording to formula I. In this example, alcohol (lxxxi) is converted tothe corresponding azide (lxxxii), which was reduced to the correspondingamine (lxxxiii). Amines (lxxxiii) were, for example, acylated, subjectedto reductive amination, and the like to make compounds according toformula I.

3-Amino-6-[3-(aminomethyl)phenyl]-N-methylpyrazine-2-carboxamide

3-Amino-6-(3-hydroxymethyl-phenyl)-pyrazine-2-carboxylic acidmethylamide (1.00 g, 3.87 mmol) was dissolved in THF (20 mL) followed bythe addition of diphenylphosphoryl azide (0.63 mL, 5.42 mmol) and DBU(0.43 mL, 5.42 mmol). It was stirred at room temperature overnight. Thereaction mixture was poured into water (100 mL), and extracted withethyl acetate (2×50 mL) then dried over anhydrous sodium sulfate andfilteration, concentration and purified by column chromatography (50%Ethylacetae/bexanes) to give3-amino-6-(3-azidomethyl-phenyl)-pyrazine-2-carboxylic acid methylamide,728 mg (66.4% yield): MS (EI) for C₁₃H₁₃N₇O₀: 284.12 (MH⁺).

3-Amino-6-(3-azidomethyl-phenyl)-pyrazine-2-carboxylic acid methylamidewas dissolved in the mixture of THF (15 mL) and H₂O (1.5 mL) followed bythe addition of triphenylphosphine (1.07 g, 4.03 mmol) and it wasstirred at room temperature overnight. The reaction mixture was pouredinto water (100 mL), and extracted with ethyl acetate (2×50 mL) thendried over anhydrous sodium sulfate and filtered, concentrated andpurified by column chromatography (50% Ethylacetae/hexanes) to give3-amino-6-(3-aminomethyl-phenyl)-pyrazine-2-carboxylic acid methylamide,564 mg (85.0% yield): MS (EI) for C₁₃H₁₅N₅O: 258.13 (MH⁺).

3-Amino-N-methyl-6-(3-{[(phenylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-Amino-6-(3-aminomethyl-phenyl)-pyrazine-2-carboxylic acid methylamide(10.0 mg, 0.04 mmol) was dissolved in acetonitrile (2 mL) followed bythe addition of TEA (11.2 μl, 0.08 mmol) and benzoyl chloride (3.50 μl,0.04 mmol). It was stirred at room temperature overnight. The reactionmixture was poured into water (10 mL), and extracted with ethyl acetate(2×10 mL) then dried over anhydrous sodium sulfate and filteration,concentration and purified by column chromatography (50%Ethylacetae/hexanes) to give3-amino-6-[3-(benzoylamino-methyl)-phenyl]-pyrazine-2-carboxylic acidmethylamide, 8.70 mg (85.0% yield): ¹H NMR (400 MHz, CDCl₃): δ 8.60 (s,1H), 8.00 (br, 1H), 7.80 (m, 4H), 7.52 (m, 4H), 7.20 (s, 1H), 6.50 (br,1H), 4.80 (m, 2H), 3.00 (d, 3H); MS (EI) for C₂₀H₁₉N₅O₂: 362.41 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

3-Amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): δ 8.60 (s, 1H), 8.00 (br, 1H), 7.80 (m, 3H),7.52 (m, 4H), 7.20 (s, 1H), 6.42 (br, 1H), 4.78 (m, 2H), 3.00 (d, 3H);MS (EI) for C₂₀H₁₈ClN₅O₂: 396.36 (MH⁺).

3-Amino-6-[3-({[(2,5-difluorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.10 (br, 1H), 8.80 (s, 1H), 8.20(m,2H),7.40 (m, 5H), 4.60 (m, 2H), 2.80 (d, 3H); MS (EI) forC₂₀H₁₇F₂N₅O₂: 398.43 (MH⁺).

3-amino-N-methyl-6-(3-{[(naphthalen-2-ylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.30 (br, 1H), 8.82 (s, 1H), 8.80 (br, 1H),8.50 (s, 1H), 8.00 (m, 5H), 7.60 (m, 2H), 7.40 (m, 2H), 4.60 (m, 2H),2.80 (d, 3H); MS (EI) for C₂₄H₂₁N₅O₂: 412.27 (MH⁺).

3-amino-6-{3-[({[3,4-dichlorophenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.40 (br, 1H), 8.82 (s, 1H), 8.80 (br, 1H),8.20 (s, 1H), 8.10 (m, 2H), 7.90 (d, 1H), 7.80 (d, 1H), 7.40 (m, 1H),7.38 (m, 1H), 4.60 (m, 2H), 2.80 (d, 3H); MS (EI) for C₂₀H₁₇Cl₂N₅O₂:430.36 (MH⁺).

3-amino-N-methyl-6-(3-{[(phenylacetyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.71 (t, 1H), 8.01 (m, 3H),7.40 (m, 1H), 7.22 (m,1H), 7.18 (m, 3H), 6.90 (m, 2H), 4.60 (d, 2H),4.40 (d, 2H), 2.80 (d, 3H); MS (EI) for C₂₁H₂₁N₅O₂: 376.46 (MH⁺).

3-amino-6-[3-({[(4-chlorophenyl)acetyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.71 (t, 1H), 8.01 (m, 2H),7.40 (m, 1H), 7.22 (m,1H), 7.18 (m, 3H), 6.90 (m, 2H), 4.60 (d, 2H),4.40 (d, 2H), 2.80 (d, 3H); MS (ED) for C₂₁H₂₀ClN₅O₂: 410.45 (MH⁺).

3-amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): δ 8.60 (s, 1H), 7.98 (br, 1H), 7.85 (m, 3H),7.70 (m, 1H), 7.60 (m,4H), 7.40 (m, 3H), 7.22(s, 2H), 6.50 (br, 1H),4.80 (d, 2H), 3.00 (d, 3H); MS (EI) for C₂₆H₂₃N₅O₂: 438.51 (MH⁺).

3-amino-6-{3-[({[2-chloro-5-(trifluoromethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): δ 8.60 (s, 1H), 7.80 (m, 3H), 7.40 (m, 3H),7.22(s, 2H), 6.60 (br, 1H), 4.80 (d, 2H), 3.00 (d, 3H); MS (EI) forC₂₁H₁₇ClF₃N₅O₂: 464.42 (MH⁺).

N-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)methyl]-1H-indole-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 11.60 (s, 1H), 8.80 (s, 1H), 8.70 (m, 1H),8.40 (m, 1H), 8.00 (m, 4H), 7.80 (m, 3H), 7.40 (m, 3H), 7.10 (m, 2H),4.60 (d, 2H), 2.80 (d, 3H); MS (EI) for C₂₂H₂₀N₆O₂: 401.48 (MH⁺).

3-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): δ 12.00 (s, 1H), 8.60 (s, 1H), 8.40 (br, 1H),7.80 (m, 3H), 7.28 (m, 5H), 7.10 (m, 2H), 4.75 (d, 2H), 3.00 (d, 3H),1.60 (br, 2H); MS (EI) for C₁₉H₁₈N₆O₃: 379.46 (MH⁺).

3-amino-6-(3-({[(1H-indole-3-ylacetyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): δ 10.85 (s, 1H), 8.80 (m, 1H), 8.40 (m, 1H),8.00 (m, 2H), 7.50 (d, 2H), 7.40 (m, 3H), 7.00 (m, 2H), 4.40 (d, 2H),3.60 (s, 3H), 3.40 (s, 2H); MS (EI) for C₂₃H₂₂N₆O₂: 414.18 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(1-methylethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.12 (br, 1H), 8.90 (s, 1H), 8.80 (br, 1H),8.50 (s, 1H), 8.38 (d, 1H), 7.80 (d, 1H), 7.50 (t, 1H), 7.20 (m, 4H),4.50 (d, 2H), 2.80(d, 3H), 1.20(m, 6H), 0.80 (m, 1H); MS (EI) forC₂₃H₂₅N₅O₂: 404.52 (MH⁺).

3-amino-N-methyl-6-(3-{[({[4-(1-methylethyl)phenyl]oxy}acetyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.90 (m, 2H), 8.72 (t, 1H), 8.05 (m, 2H),7.40 (m, 1H), 7.20 (m, 3H), 6.90 (d, 2H), 4.60 (s, 2H), 4.40(d, 2H),2.80(d, 3H), 1.20(m, 6H), 0.80 (m, 1H); MS (EI) for C₂₄H₂₇N₅O₃: 434.51(MH⁺).

3-amino-6-{3-[({[(4-aminophenyl)thio]acetyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.90 (m, 2H), 8.70 (t, 1H), 8.00 (m, 2H),7.40 (m, 1H), 7.18 (m, 3H), 6.50 (d, 2H), 5.20 (s, 2H), 4.40 (d, 2H),2.80 (d, 3H); MS (EI) for C₂₁H₂₂N₆O₂S: 423.44 (MH⁺).

3-amino-6-[3-({[(4-iodophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.20 (m, 1H), 8.90 (m, 2H), 8.12 (m, 2H),7.80 (m, 2H), 7.70 (m, 2H), 7.40 (m, 2H), 4.50 (d, 2H), 2.80 (d, 3H); MS(EI) for C₂₀H₁₈N₅O₂I: 488.35 (MH⁺).

3-amino-N-methyl-6-[3-({[(4-pentylphenyl)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.00 (m, 1H), 8.90 (m, 2H), 8.12 (m, 2H),7.80 (m, 2H), 7.40 (m, 4H), 4.60 (d, 2H), 3.40 (d, 3H), 1.60 (m, 2H),1.20 (m, 5H), 0.80 (m, 4H); MS (EI) for C₂₅H₂₉N₅O₂: 432.55 (MH⁺).

3-amino-6-(3-{[(1,3-benzodioxol-5-ylcarbonyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.78 (m, 2H), 8.50 (br, 1H), 8.08 (d, 1H),7.98 (s, 1H), 7.42 (t, 1H), 7.20 (d, 1H), 6.80 (m, 3H), 4.40 (d, 2H),2.80 (d, 3H); MS (EI) for C₂₁H₁₉N₅O₄: 406.15 (MH⁺).

3-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.10 (br, 1H), 8.90 (s, 1H), 8.80 (br, 1H),8.50 (s, 1H), 8.40 (d, 1H), 7.82 (d, 1H), 7.60 (t, 1H), 7.35 (m, 4H),4.50 (d, 2H), 2.80 (d, 3H); MS (EI) for C₂₄H₂₇N₅O₂: 418.52 (MH⁺).

3-amino-N-methyl-6-(3-{[({1-[5-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 8.80 (m, 2H), 8.62 (m, 1H), 8.40 (t, 1H),8.00 (m, 2H), 7.40 (t, 1H), 7.20 (d, 1H), 7.00 (d, 1H), 4.60 (d, 2H),4.38 (d, 2H), 2.98 (t, 2H), 2.80 (d, 3H), 1.80 (m, 2H), 1.60 (m, 2H),1.20 (m, 1H); MS (EI) for C₂₄H₂₅N₈O₂F₃: 515.51 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(1-methylethyl)phenyl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.00 (br, 1H), 8.90 (m, 2H), 8.12 (m, 2H),7.82 (d, 1H), 7.35 (m, 4H), 4.60 (d, 2H), 2.90 (m, 1H), 2.80 (d, 3H),1.20 (d, 6H); MS (EI) for C₂₃H₂₅N₅O₂: 404.50 (MH⁺).

3-amino-6-[3-({[(4-butylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.10 (br, 1H), 8.90 (m, 2H), 8.50 (s, 1H),8.40 (d, 1H), 7.82 (d, 1H), 7.60 (m, 1H), 7.20 (m, 4H), 4.60 (d, 2H),2.80 (d, 3H), 2.60 (m, 2H), 1.60 (m, 2H), 1.32 (m, 2H), 0.90 (m, 3H); MS(EI) for C₂₄H₂₇N₅O₂: 418.49 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.60 (s, 1H), 9.20 (br, 1H), 8.90 (m, 2H),8.60 (s, 1H), 8.40 (d, 1H), 8.18 (d, 2H), 7.98 (d, 1H), 7.58 (m, 3H),4.60 (d, 2H), 2.80 (d, 3H); MS (EI) for C₂₂H₁₉N₇O₂S: 446.42 (MH⁺).

3-amino-N-methyl-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.20 (s, 1H), 8.90 (m, 2H), 8.60 (s, 1H),8.40 (d, 1H), 7.98 (d, 1H), 7.58 (m, 7H), 7.18 (d, 1H), 4.60 (d, 2H),2.80 (d, 3H); MS (EI) for C₂₄H₂₁N₅O₂S: 444.46 (MH⁺).

3-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.10 (s, 1H), 8.90 (m, 2H), 8.00 (m, 4H),7.40 (m, 4H), 4.60 (d, 2H), 2.80 (d, 3H); MS (EI) for C₂₄H₂₇N₅O₂: 418.51(MH⁺).

3-amino-N-methyl-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.20 (br, 1H), 8.90 (m, 2H), 8.50 (m, 3H),7.60 (m, 7H), 6.50 (s, 1H), 4.60 (d, 2H), 2.80 (d, 3H); MS (EI) forC₂₃H₂₁N₇O₂: 428.48 (MH⁺).

Example 54

Scheme 19 depicts a strategy for making exemplary compounds according toformula I where A is an oxazole. Compound (lxxxiv) is protected as theTBS-ether (lxxxv). The ester function of (lxxxv) is reduced to thecorresponding alcohol, (lxxxvi), and reoxidized to the correspondingaldehyde, (lxxxvii). Aldehyde (lxxxvii) was converted to oxazole(lxxxviii) as described below.

{3-[5-amino-6-(1,3-oxazol-5-yl)pyrazin-2-yl]phenyl}methanol: Methyl3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carboxylate (200 mg, 0.77mmol) was dissolved in DMF followed by addition of tert-butylsilylchloride (0.14 g, 0.93 mmol) and imidazole (63 mg, 9.25 mmol). Thismixture was stirred at room temperature under nitrogen for overnight.The reaction mixture was poured into water (75 mL), and extracted withethyl acetate (2×50 mL) then dried over anhydrous sodium sulfate andfilteration, concentration to give crude silyl ether product, 170 mg(59.0%). It was dissolve in THF followed by addition of lithium aluminumhydride (1.0 M solution in THF, 0.9 ml, about 2.0 equiv.) and it wasstirred at room temperature for 5 hrs. It was directly subjected tooxidation reaction with MnO₂. Crude compounds was dissolved in acetonefollowd by the addition of MnO₂ (730 mg, 20 equiv.). It was refluxed for1 hr then dried over anhydrous sodium sulfate and filteration,concentration to give crude aldehyde, 94.0 mg (66.0%). The aldehyde wasdissolved in MeOH (20 ml), followed by tosylmethylisocyanide (56.0 mg,2.87 mmol) and K₂CO₃ (40.0 mg, 2.87 mmol). This reaction mixture wasrefluxed for 4 hrs. and then followed usual aqeous work up and it wastreated with HCl to give the desired oxazole, 62.0 mg (84.4%). ¹H NMR(400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.01 (s, 1H), 7.80 (s, 1H), 7.20 (m,4H), 4.70 (m, 2H); MS (EI) for C₁₄H₁₂N₄O₂: 267.14 (MH⁺).

Example 555-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(1,3-oxazol-5-yl)pyrazin-2-amine

Using the {3-[5-Amino-6-(1,3-oxazol-5-yl)pyrazin-2-yl]phenyl}methanol,Mitsunobu reactions were carried out as outlined in Scheme 15 above tomake compounds according to formula I.

To a solution of oxazole (lxxxviii) (1 (62.0 mg, 2.31 mmol) in benzene(0.5 M solution) was addedN-[(1S)-2,3-dihydro-1H-inden-1-yl]2,4-dinitrobenzenesulfonamide (42.0mg, 1.15 mmol), triphenylphosphine (57.7 mg, 2.19 mmol) and DEAD (0.034mL, 2.31 mmol) and the mixture was allowed to stir at room temperatureovernight. The solvent was removed and directly subjected to columnchromatography purification (50% ethylacetate/hexanes) to give theintermediate sulfonamide, 123 mg (84.8% yield), which was treated withn-propylamine (20 equiv.) and purified by MPLC to give5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(1,3-oxazol-5-yl)pyrazin-2-amine,100 mg (81.3% yield): 1H NMR (400 MHz, d4-MeOH): δ 8.58 (s, 1H), 8.40(s, 1H), 8.00 (s, 1H), 7.82 (d, 1H), 7.80 (s, 1H), 7.40 (m, 4H), 7.20(4H), 4.35(m, 1H), 3.90 (m, 2H), 3.10 (m, 1H), 2.80 (m, 1H), 2.40 (m,1H), 1.98 (m, 1H); MS (EI) for C₂₃H₂₁N₅O: 384.15 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

1-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-yl]ethanone:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.40 (s, 1H), 7.98 (d, 1H),7.80 (m, 2H), 7.40 (m, 3H), 7.20 (m, 3H), 4.21 (m, 1H), 3.82 (m, 2H),3.10 (m, 1H), 2.81 (m, 1H), 2.61 (m, 3H), 2.38 (m, 1H), 1.97 (m, 1H); MS(EI) for C₂₂H₂₂N₄O: 359.15 (MH⁺).

[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-yl](phenyl)methanone:¹H NMR (400 MHz, d4-MeOH): δ 8.80 (s, 1H), 8.00 (d, 2H), 7.98 (s, 1H),7.80 (m, 1H), 7.40 (m, 8H), 7.20 (m, 4H), 4.40 (m, 1H), 3.90 (m, 2H),3.10 (m, 1H), 2.85 (m, 1H), 2.40 (m, 1H), 2.05 (m, 1H); MS (EI) forC₂₇H₂₄N₄O: 421.20 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine:¹H NMR (400 MHz, d4-MeOH): δ 10.1 (br, 1H), 9.00 (m, 3H), 8.70 (d, 1H),8.30 (d, 1H), 7.91 (d, 1H), 7.40 (m, 7H), 4.81 (br, 1H), 4.35 (br, 1H),4.71 (m, 1H), 3.21 (m, 1H), 2.91 (m, 1H), 2-.51 (m, 1H); MS (EI) forC₂₇H₂₄N₈: 461.16 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (s, 1H), 8.40 (br, 1H), 8.21 (m, 1H),7.60 (m, 3H), 7.40 (m, 3H), 4.35 (s, 2H), 3.71 (m, 6H), 3.12 (m, 2H),2.70 (m, 1H), 2.40 (m, 2H), 2.18 (m, 3H); MS (EI) for C₂₇H₃₀N₈: 467.41(MH⁺).

5-{3-[(2,3-dihydro-1H-inden-1-ylamino)methyl]phenyl}-3-(3-piperidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine:¹H NMR (400 MHz, d4-MeOH): 6 8.60 (d, 2H), 8.18 (d, 1H), 7.79 (d, 1H),7.60 (m, 2H), 7.40 (m, 3H), 4.40 (s, 2H), 3.60 (m, 6H), 3.12 (m, 1H),3.05 (m, 1H), 2.67 (m, 1H), 2.42 (m, 1H), 2.18 (m, 1H), 2.10 (m, 3H); MS(EI) for C₂₇H₃₀N₈: 467.18 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine:¹H NMR (400 MHz, d4-MeOH): δ 8.60 (d, 2H), 8.18 (d, 1H), 7.79 (d, 1H),7.60 (m, 2H), 7.40 (m, 3H), 4.40 (s, 2H), 3.60 (m, 5H), 3.30 (m, 1H),3.18 (m, 1H), 3.02 (m, 1H), 2.62 (m, 1H), 2.41 (m, 1H), 2.38 (m, 1H),2.00 (m, 3H); MS (EI) for C₂₇H₃₀N₈: 467.33(MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine:¹H NMR (400 MHz, d4-MeOH): δ 8.60 (d, 2H), 8.18 (d, 1H), 7.79 (d, 1H),7.60 (m, 2H), 7.40 (m, 3H), 4.40 (s, 2H), 3.60 (m, 5H), 3.30 (m, 1H),3.18 (m, 1H), 3.02 (m, 1H), 2.62 (m, 1H), 2.41 (m, 1H), 2.38 (m, 1H),2.00 (m, 3H); MS (EI) for C₂₇H₃₀N₈: 467.33 (MH⁺).

Example 56

Scheme 20 depicts a strategy for making exemplary compounds according toformula I where A is a triazole. Compound (lxxxix) is converted to thecorresponding triazole, (xc), for example, as described below.

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-phenyl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine:A solution of sodium ethoxide (19 mg, 0.27 mmol) in anhydrous ethanol (2mL) was added to a solution of benzenecarboximidamide hydrochloridehydrate (31.35 mg, 0.2 mmol) in anhydrous ethanol (3 mL) at roomtemperature. The mixture was stirred at room temperature for 45 min. andfiltered. To the ethanol filterate was added3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carbohydrazide(50 mg, 0.13 mmol) and the resulting solution was heated to refluxovernight. The solvent was removed and purified by MPLC to give compound1 (12.5 mg 21.3% yield): ¹H NMR (400 MHz, d6-DMSO): δ 10.0 (s, 1H), 9.00(m, 3H), 8.70 (d, 1H), 8.30 (d, 1H), 7.70 (d, 1H), 7.35 (m, 8H), 4.81(br, 1H), 4.35 (br, 2H), 3.62 (m, 1H), 3.55 (m, 1H), 3.20 (m, 1H), 2.95(m, 1H); MS (EI) for C₂₈H₂₅N₇: 460.10 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine: ¹H NMR(400 MHz, d6-DMSO): δ 10.0 (br, 1H), 9.00 (m, 3H), 8.70 (d, 1H), 8.30(d, 1H), 7.90 (d, 1H), 7.40 (m, 7H), 4.81 (br, 1H), 4.40 (br, 2H), 3.70(m, 1H), 3.55 (m,1H), 3.25 (m, 1H), 2.95 (m, 1H), 2.50 (m, 1H); MS (EI)for C₂₇H₂₄N₈: 461.12 (MH⁺).

Example 57

Scheme 21 depicts a strategy for making imidoates according to formulaI. Nitrile (xci) is converted to the corresponding imidoate, (xcii), forexample, as described below. Such imidoates are generally used asintermediates to make, for example, compounds according to formula Iwhere A is a triazole, or oxadiazole, and the like as one skilled in theart could readily perform. For example addition ofbenzenecarboximidamide to imidoate (xcii) under appropriate conditions(e.g. heat and dehydrative conditions) would give the correspondingtriazole derivative (xciii). Some exemplary compounds are listed in thisexample.

Ethyl 3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carboximidoate: Asuspension of 3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile(500 mg, 2.21 mmol) in ethanol was cooled by ice bath. Dry hydrogenchloride gas was bubbled into the reaction mixture for 2 or 3 hours.After gas addition was stopped, the solution was placed in arefrigerator overnight. The solution was filtered and evaporated toafforded compound 1 (452 mg, 75.3% yield): ¹H NMR (400 MHz, d6-DMSO): δ9.00 (s, 1H), 8.15 (s, 1H), 8.00 (m, 1H), 7.42 (m, 3H), 4.80 (q, 2H),4.62 (s, 21H), 1.60 (t, 1H); MS (EI) for C₁₄H₁₆N₄O: 273.23 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

2-({3-Amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2-yl}carbonyl)-N-phenylhydrazinecarboxamide: ¹H NMR (400 MHz, d6-DMSO): δ 10.42 (s, 1H), 8.20 (m, 3H),7.40 (m, 8H), 6.95 (m, 1H), 5.20 (t, 1H), 4.60 (m, 2H); MS (EI) forC₁₉H₁₈N₆O₃: 379.13 (MH⁺).

3-Amino-N-hydroxy-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carboximidamide:¹H NMR (400 MHz, d6-DMSO): δ 10.23 (s, 1H), 8.60 (s, 1H), 8.00 (m, 2H),7.40 (m, 2H), 6.15 (s, 1H), 5.21 (t, 1H), 4.60 (m, 2H); MS (EI) forC₁₂H₁₃N₅O₂: 260.21 (MH⁺).

{3-[5-Amino-6-(3-pyridin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d6-DMSO): δ 9.60 (s, 1H), 8.92 (m, 3H), 8.20 (m, 2H),7.90 (m, 2H), 7.40 (m, 2H), 5.21 (t, 1H), 4.60 (m, 2H); MS (EI) forC₁₈H₁₅N₇O: 346.11 (MH⁺).

(3-{5-Amino-6-[3-(4-chlorophenyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol:¹H NMR (400 MHz, d6-DMSO): δ 8.70 (s, 1H), 8.20 (m, 3H), 7.80 (m, 3H),7.40 (m, 3H), 4.60 (m, 2H), 4.40 (s, 1H); MS (EI) for C₁₉H₁₅N₆OCl:379.07 (MH⁺).

{3-[5-amino-6-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d4-MeOH): δ 8.80 (m, 5H), 8.10 (m, 3H), 7.50 (m, 2H),7.40 (m, 3H), 4.72 (s, 2H) MS (EI) for C₁₈H₁₅N₇O: 346.24 (MH⁺).

{3-[5-amino-6-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d4-MeOH): δ 8.50 (s, 5H), 8.05 (s, 3H), 7.90 (m, 1H),7.40 (m, 2H), 4.60 (s, 2H), 2.30 (m, 4H), 1.21 (m, 5H); MS (EI) forC₁₈H₁₂N₇O: 352.28 (MH⁺).

{3-[5-amino-6-(3-piperidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d6-DMSO): δ 9.50 (dd, 2H), 8.78 (s, 1H), 8.20 (m, 2H),7.40 (m, 2H), 4.60 (s, 2H), 3.32 (m, 4H), 1.67 (m, 5H); MS (EI) forC₁₈H₁₂N₇O: 352.28 (MH⁺).

{3-[5-amino-6-(3-pyrrolidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d6-DMSO): δ 8.60 (s, 1H), 8.18 (s, 1H), 8.00 (d, 1H),7.45 (m, 2H), 4.70 (s, 2H), 3.97 (m, 1H), 3.78 (m, 2H), 3.50 (m, 2H),2.60 (m, 1H), 2.41 (m, 1H); MS (EI) for C₁₇H₁₉N₇O: 338.30 (MH⁺).

{3-[5-amino-6-(3-pyridin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d6-DMSO): δ 8.91 (m, 2H), 8.56 (d, 1H), 8.40 (t, 1H),8.18 (m, 2H), 7.81 (t, 1H), 7.42 (m, 2H), 4.70 (s, 2H); MS (EI) forC₁₈H₁₅N₇O: 346.22 (MH⁺).

{3-[5-amino-6-(3-piperidin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d6-DMSO): δ 9.85 (m, 1H), 9.40 (m, 1H), 8.80 (s, 1H),8.18 (m, 2H), 7.42 (m, 2H), 4.62 (s, 2H), 3.40 (m, 3H), 1.62 (m, 6H); MS(EI) for C₁₈H₂₁N₇O: 461.16 (MH⁺).

{3-[5-amino-6-(3-morpholin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol:¹H NMR (400 MHz, d6-DMSO): δ 9.85 (m, 1H), 9.60 (m, 1H), 8.80 (s, 1H),8.18 (m, 2H), 7.42 (m, 2H), 5.12 (d, 1H), 4.62 (s, 2H); MS (EI) forC₁₇H₁₉N₇O₂: 354.15 (MH⁺).

[3-(5-amino-6-{3-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methanol:¹H NMR (400 MHz, d4-MeOH): δ 9.60 (s, 1H), 8.20 (s, 1H), 8.10 (m, 2H),4.72 (s, 2H), 3.62(m, 2H), 3.54 (m, 2H), 3.10 (m, 1H), 2.38 (m, 1H),2.00 (m,3H); MS (EI) for C₁₈H₂₁N₇O: 352.17 (MH⁺).

[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methanol:¹H NMR (400 MHz, d4-MeOH): δ 9.60 (s, 1H), 8.20 (s, 1H), 8.10 (m, 2H),4.72 (s, 2H), 3.62(m, 2H), 3.54 (m, 2H), 3.10 (m, 1H), 2.38 (m, 1H),2.00 (m,3H); MS (EI) for C₁₈H₂₁N₇O: 352.17 (MH⁺).

Example 58

Scheme 22 depicts another strategy for making exemplary compoundsaccording to formula I where A is a triazole. Boronic acid-acyl chlorideintermediate (xciv) is coupled with amine (xcv) to give amide (xcvi).Intermediate (xcvi) is coupled to a bromo-pyrazine, for example, to giveintermediate (xcvii). The nitrile group of (xcvii) is converted to thecorresponding triazole to yield (xcviii), for example, as more fullydescribed below. Intermediate (xcvii) can also be used to make otherheterocycles for A, according to formula I. Included in this example areother various triazole syntheses that generally start from acorresponding nitrile precursor.

3-(5-amin-6-cyano-pyrazin-2-yl)-N-[(4-chloro-2-fluorophenyl)methyl]benzamide

4-Carbonyl chloride phenylboronic aicd (35 0 mg, 1.90 mmol) was added toTHF followed by addition of 4-chloro-2-fluoro benzylamine (466 mg, 2.37mmol) and triethylamine (400 μl, 2.85 mmol). This mixture was stirred atroom temperature under nitrogen overnight. The reaction mixture waspoured into water (75 mL), and extracted with ethyl acetate (2×50 mL)then dried over anhydrous sodium sulfate and filteration, concentrationto give crude reduction product, 525 mg (90.0% yield). Subsequently itwas dissolved in DMF followed by addition of3-amino-6-bromo-pyrazine-2-carbonitrile (169 mg, 0.85 mmol),Pd(dppf)CH₂Cl₂ (69.2 mg, 10 mol %) and triethylamine (118 μl, 2.12mmol). It was heated to 80° C. for 16 hrs and quenched with H₂O andextracted with ethylacetate then dried over anhydrous sodium sulfate andfilteration, concentration to give crude reduction product (275 mg,85.0% yield): MS (EI) for C₁₉H₁₃ClFN₅O: 382.14 (MH⁺).

3-(5-anmino-6{3-[(3S)-piperidin-3-yl]-1H-1,2,4-traiazol-5-yl}pyrazine-2-yl)-N[4-chloro-2-fluorophenyl)methyl]benzamide:3-(5-Amino-6-cyano-pyrazin-2-yl)-N-(4-chloro-2-fluoro-benzyl)-benzamide(238.0 mg, 0.63 mmol) and 1,1-dimethylethyl(3S)-3-(hydrazinocarbonyl)piperidine-1-carboxylate (460 mg, 1.89 mmol)was combined together and it was heated to 180° C. for 1 or 2 hrs. Thereaction mixture was poured into water (575 mL), and extracted withethyl acetate (2×35 mL) then dried over anhydrous sodium sulfate andfilteration, concentration and purified by MPLC to give3-[5-amino-6-(5-piperidin-3-yl-2H-[1,2,4]triazol-3-yl)-pyrazin-2-yl]-N-(4-chloro-2-fluoro-benzyl)-benzamide(206.0 mg, 65.0% yield): ¹H NMR (400 MHz, d4-MeOH): δ 8.60 (d, 2H), 8.20(d, 1H), 7.82 (d, 1H), 7.58 (t, 1H), 7.38 (t, 1H), 7.15 (m, 2H), 4.60(s,2H), 3.62 (m, 1H), 3.40(m, 3H), 2.99 (m, 1H), 2.37 (m, 1H), 1.98 (m,3H); MS (EI) for C₂₅H₂₄N₈OFCl: 507.03 (MH⁺).

1-(1,1-dimethylethyl) 3-ethyl (3S)-piperidine-1,3-dicarboxylate: To anice-cooled, stirred solution of (S)-(+)-ethyl nipecotate (3.95 g, 25.1mmnol, from Sigma-Aldrich) in 20 mL of THF, was added 8.21 g (37.6 mmol,1.5 eq.) of di-tert-butyl dicarbonate. The ice bath was removed, and thereaction stirred at room temperature for 19 h and concentrated. Thecrude oil was purified by silica gel chromatography (55 mm column, 5inches of silica gel) using 15% EtOAc in hexanes as eluent.Concentration afforded 6.28 g (97.2% yield) of product as an oil.

1,1-dimethylethyl (3S)-3-(hydrazinocarbonyl)piperidine-1-carboxylate: Toa solution of 6.28 g (24.4 mmol) of 1-(1,1-dimethylethyl) 3-ethyl(3S)-piperidine-1,3-dicarboxylate in 25 mL of MeOH was added 7.11 mL ofhydrazine monohydrate (146 mmol, 5.98 eq.). The mixture was refluxed for2 h and concentrated. The reaction could be monitored by LC/MS on areversed-phase column at 220 nm wavelength. The crude material was takenup in EtOAc, and washed with 2×H₂O, 1× sat. aqueous NaCl, and dried overNa₂SO₄. Filtration and concentration afforded 3.21 g of product (54.0%yield) as a viscous oil. The product was ca. 80% pure by hplc analysisand was used as such without further purification.

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,6-difluorophenyl)methyl]benzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.60 (d, 2H), 8.38 (d, 1H), 7.88 (d, 1H),7.60 (t, 1H), 7.38 (m, 2H), 7.15 (t, 1H), 4.80 (s, 2H), 3.78 (m, 1H),3.50 (m, 3H), 3.15 (m, 1H), 2.37 (m, 1H), 1.98 (m, 3H); MS (EI) forC₂₅H₂₄N₈OF₂: 491.08 (MH⁺).

3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5yl}pyrazin-2-yl)-N-[(2-chloro-6-fluorophenyl)methyl]benzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.60 (d, 2H), 8.32 (d, 1H), 7.82 (d, 1H),7.60 (t, 1H), 7.40 (t, 1H), 7.00 (m, 2H), 4.70 (s, 2H), 3.78 (m, 1H),3.50 (m, 3H), 3.05 (m, 1H), 2.37 (m, 1H), 2.00 (m, 3H); MS (EI) forC₂₅H₂₄N₈OFCl: 507.03 (MH⁺).

3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,5-dichlorophenyl)methyl]benzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.75 (d, 2H), 8.38 (d, 1H), 7.95 (d, 1H),7.62 (t, 1H), 7.40 (m, 2H), 7.25 (d, 1H), 4.62 (s, 2H), 3.78 (m, 1H),3.50 (m, 3H), 3.05 (m, 1H), 2.41 (m, 1H), 2.00 (m, 3H); MS (EI) forC₂₅H₂₄N₈OCl₂: 523.19 (M⁺).

3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(3,4-dichlorophenyl)methyl]benzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.70 (d, 2H), 8.38 (d, 1H), 7.95 (d, 1H),7.62 (t, 1H), 7.58 (s, 1H), 7.42 (d, 2H), 7.38 (d, 1H), 4.60 (s, 2H),3.72 (m, 1H), 3.50 (m, 3H), 3.05 (m, 1H), 2.38 (m, 1H), 2.00 (m, 3H); MS(EI) for C₂₅H₂₄N₈OCl₂: 523.19 (M⁺).

(3-{5-Amino-6-[3-(2-thienyl)-1H-1,2,4-triazol-5-yl}pyrazin-2-yl]phenyl)methanol

To a solution of3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile (149 mg, 0.74mmol) was added thiophene-2-carboxylic acid hydrazide (94 mg, 0.66mmol), sodium methoxide (53 mg, 0.996 mmol) in MeOH (5 mL). After refluxfor 4 days, the reaction mixture was extracted with ethyl acetate (10mL×3) and dried over MgSO₄. Filteraction and concentration in vacuo gavea crude product, which was purified by preparative HPLC (0.1% TFA inwater/0.1% TFA in CH₃CN). The product fractions were neutralized byaqueous saturated sodium bicarbonate solution and partitioned with ethylacetate. The aqueous phase was extracted once with additional ethylacetate. The combined organic layers were washed with saturated aqueoussodium chloride then dried over anhydrous magnesium sulfate. Filtrationand concentration in vacuo gave the(3-{5-amino-6-[3-(2-thienyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl }phenyl)methanol (14 mg, yield): ¹H NMR (400 MHz, CD₃OD): δ 8.65 (s, 1H),8.14 (s, 1H), 8.02 (d, 1H), 7.77 (m, 1H), 7.53 (m, 1H), 7.47 (m, 1H),7.38 (m, 1H), 7.17 (m, 1H), 4.72 (s, 2H); MS (EI) for C₁₇H₁₄N₆O: 351.10(MH⁺).

(3-{5-Amino-6-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol:To a solution of of3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile (250 mg, 1.11mmol) was added 2-aminoisonicotinic acid hydrazide (311 mg, 2.04 mmol).After being heated at 180° C. for 90 min, the reaction mixture wasdissolved in DMF and washed with water, ethyl acetate (10 mL×3). Theaqueous phase was extracted once with additional ethyl acetate. Thecombined organic layers were washed with saturated aqueous sodiumchloride then dried over anhydrous magnesium sulfate. Filtration andconcentration in vacuo gave a crude oil, which was purified bypreparative HPLC to yield(3-{5-amino-6-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol(23.2 mg, 5.7% yield): ¹H NMR (400 MHz, DMSO-d6): δ 8.80 (s, 1H), 8.15(s, 1H), 8.10 (m, 1H), 7.70 (m, 2H), 7.43 (m, 2H), 7.20 (m, 1H), 6.10(s, 2H), 5.25 (m, 1H) 4.60 (m, 1H); MS (EI) for C₁₈H₁₆N₈O: 361.11 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following 1H-1,2,4-triazole compounds ofthe invention were prepared:

5-{3-[(2,3-Dihydro-1H-inden-1-ylamino)methyl]phenyl}-3-{3-[3-(methyloxy)phenyl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine: ¹HNMR (400 MHz, DMSO-d6): δ 8.82 (s, 1H), 8.38 (m, 2H), 7.82 (m, 1H), 7.76(d, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.43 (m, 1H), 7.35 (m, 3H), 7.11(m, 1H), 4.75 (bs, 1H), 4.23 (m, 2H), 3.87 (s, 3H), 3.18 (m, 1H), 2.90(m, 1H), 2.45 (m, 1H), 2.30 (m, 1H); MS (EI) for C₂₉H₂₇N₇O: 490.14(MH⁺).

3-{5-Amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}-N-[(2-chloro-6-fluorophenyl)methyl]benzamide:¹H NMR (400 MHz, DMSO-d₆): δ 10.40 (s, 1H), 8.97 (m, 2H), 8.57 (s, 1H),8.40 (m, 1H), 7.87 (m, 1H), 7.80 (bs, 1H), 7.55 (m, 1H), 7.37 (m, 2H),7.22 (m, 1H), 4.63 (s, 2H), 3.78 (m, 1H), 3.43 (m, 2H), 3.23 (m, 1H),3.00 (m, 1H), 2.97 (s, 3H), 2.22 (m, 1H), 2.01 (m, 2H), 1.61 (m, 1H); MS(EI) for C₂₆H₂₆N₈OFCl: 521.02 (MH⁺).

3-(5-Amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(4-chloro-2-fluorophenyl)methyl]benzamide:¹H NMR (400 MHz, CD₃OD): δ 8.68 (s, 2H), 8.29 (d, 1H), 7.93 (d, 1h),7.62 (t, 1H), 7.45 (t, 1H), 7.20 (m, 2H), 4.67 (s, 2H), 3.75 (m, 1H),3.47 (m, 3H), 3.12 (m, 2H), 2.33 (m, 1H), 2.03 (m, 2H); MS (EI) forC₂₅H₂₄N₈OFCl: 507.02 (MH⁺).

3-(5-Amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,4-difluorophenyl)methyl]benzamide:¹H NMR (400 MHz, DMSO-d₆): δ 9.23 (m, 1H), 8.89 (m, 2H), 8.65 (s, 1H),8.42 (m, 1H), 7.89 (m, 1H), 7.78 (bs, 1H), 7.60 (m, 1H), 7.45 (m, 1H),7.26 (m, 1H), 7.08 (m, 1H), 4.54 (d, 2H), 3.30 (m, 2H), 3.18 (m, 1H),2.96 (m, 1H), 2.19 (m, 1H), 1.87 (m, 3H); MS (EI) for C₂₅H₂₄N₈OF₂:491.08 (MH⁺).

3-(5-Amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(3,4-difluorophenyl)methyl]benzamide:¹H NMR (400 MHz, DMSO-d6): δ 9.42 (m, 1H), 9.02 (m, 2H), 8.90 (s, 1H),8.71 (s, 1H), 8.41 (m, 1H), 7.90 (m, 1H), 7.78 (m, 1H), 7.60 (m, 1H),7.42 (m, 2H), 7.23 (m, 1H), 4.51 (d, 2H), 3.57 (m, 1H), 3.29 (m, 2H),3.20 (m, 1H), 2.90 (m, 1H), 2.20 (m, 1H), 1.85 (m, 3H); MS (EI) forC₂₅H₂₄N₈0F₂: 491.08 (MH⁺).

3-[3-(2-Aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]-5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-amine:¹H NMR (400 MHz, DMSO-d6): δ 8.99 (s, 1H), 8.85 (s, 1H), 7.31 (d, 2H),8.07 (d, 1H), 7.85 (d, 1H), 7.73 (s, 1H), 7.55 (m, 2H), 7.37 (d, 1H),7.31 (m, 1H), 4.83 (m, 1H), 4.32 (m, 2H), 3.25 (m, 1H), 2.91 (m, 1H),2.43 (m, 1H); MS (EI) for C₂₇H₂₅N₉: 476.07 (MH⁺).

(3-{5-amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol:¹H NMR (400 MHz, d₆-DMSO): 10.34 (br s, 1H), 8.77 (s, 1H), 8.11 (s, 1H),8.07 (d, 1H), 7.68 (br s, 2H), 7.42 (m, 1H), 7.34 (d, 1H), 4.58 (s, 2H),3.75 (m, 1H), 3.45 (m, 1H), 3.38 (m, 1H), 3.22 (m, 1H), 2.99 (m, 1H),2.82 (m, 3H), 2.19 (m, 1H), 1.95 (m, 2H), 1.68 (m, 1H); MS (EI) forC₁₉H₂₃N₇O: 366.2 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-amine:¹H NMR (400 MHz, d₆-DMSO): 10.40 (br s, 1H), 9.76 (br s, 1H), 8.85 (s,1H), 8.67 (s, 1H), 8.25 (m, 1H), 7.82 (d, 1H), 7.75 (br s, 2H), 7.53 (m,2H), 7.36 (m, 2H), 7.30 (m, 1H), 4.83 (m, 1H), 4.27 (m, 2H), 3.76 (m,1H), 3.46 (m, 1H), 3.40 (m, 1H), 3.20 (m, 2H), 2.94 (m, 2H), 2.82 (m,3H), 2.38 (m, 1H, 2.20 (m, 1H), 1.96 (m, 2H), 1.67 (m, 1H); MS (EI) forC₂₈H₃₂N₈: 481.2 (MH⁺).

Example 59

Scheme 23 depicts two exemplary compounds, (xcix) and (c), according toformula I, which are useful as intermediates to synthesize othercompounds of the invention. Exemplary syntheses of such compoundsfollows, and generally can also be used to make other heterocycles(besides triazoles) for A, according to formula I.

1,1-Dimethylethyl(3R)-3-(5-{3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2-yl}-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate:3-Amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile (514.0 mg,2.27 mmol) and 1,1-dimethylethyl(3S)-3-(hydrazinocarbonyl)piperidine-1-carboxylate (1.66g, 6.83 mmol)were combined together and heated to 180° C. for 1-2 h. The reactionmixture was poured into water (100 mL), and extracted with ethyl acetate(2×35 mL) then dried over anhydrous sodium sulfate and filteration,concentration and purified by MPLC to give 1,1-dimethylethyl(3R)-3-(5-{3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2-yl}-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate. (655.0 mg, 64.2%yield): MS (EI) for C₂₃H₂₉N₇O₃: 452.29 (MH⁺).

1,1-dimethylethyl(3R)-3-(5-{3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2-yl}-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate:1,1-dimethylethyl(3R)-3-(5-{3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2-yl}-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate(655.0 mg, 1.45 mmol) was dissolved in THF (20 mL) followed by theaddition of diphenylphosphoryl azide (0.45 mL, 2.03 mmol) and DBU (0.31mL, 2.03 mmol). It was stirred at room temperature overnight. Thereaction mixture was poured into water (100 mL), and extracted withethyl acetate (2×50 mL) then dried over anhydrous sodium sulfate andfilteration, concentration and purified by column chromatography (50%Ethylacetae/hexanes) to give the intermediate azide, 458.0 mg (66.4%, MS(EI) for C₂₃H₃₀N₈O₂: 451.27 (MH⁺), which was dissolved in the mixture ofTHF (15 mL) and H₂O (1.5 mL) followed by the addition oftriphenylphosphine (0.76g, 2.88 mmol) and it was stirred at roomtemperature overnight. The reaction mixture was poured into water (100mL), and extracted with ethyl acetate (2×50 mL) then dried overanhydrous sodium sulfate. The extracts were filtered, concentrated, andpurified by column chromatography (O to 100% MeOH in Ethyl acetate) togive1,1-dimethylethyl(3R)-3-(5-{3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2-yl}-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate,368.0 mg (85.0% yield).

5-[3-(Aminomethyl)phenyl]-3-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine:To a solution of1,1-dimethylethyl(3R)-3-(5-{3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2-yl}-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate(50.0 mg, 0.11 mmol) in MeOH (3.0 mL) was added 4.0M HCl in dioxane (15mL) and stirred it overnight at room temperature. All solvent wasevaporated under vacuum to give compound 1, 28.0 mg (72.0% yield): ¹HNMR (400 MHz, d4-MeOH): δ 8.62 (s, 1H), 8.38 (s, 1H), 8.21 (d, 1H), 7.60(m, 1H), 4.22(s, 2H), 3.65 (m, 1H), 3.42 (m, 3H), 3.16 (m, 1H), 2.38 (m,1H), 2.00 (m, 3H); MS (EI) for C₁₈H₂₂N₈: 351.27 (MH⁺).

Example 60

Generally, intermediates (xcix) and (c) (see Scheme 23 above) are usedto attach Y (according to formula I) to make compounds of the invention,and thereby also establish X in many examples. Included in this exampleis description of such syntheses.

N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-2-chlorobenzamideHCl: Intermediate 2 (50.0 mg, 0.11 mmol) was dissolved in DMF (5mL)followed by the addition of HOBT (30.0 mg, 0.22 mmol) and EDCI (43.0 mg,0.22 mmol). It was stirred at room temperature overnight. The reactionmixture was poured into water (100 mL), and extracted with ethyl acetate(2×50 mL) then dried over anhydrous sodium sulfate and filtered,concentrated and purified by column chromatography (50%Ethylacetae/hexanes) and subsequently it was treated with 4.0 M HCl indioxane (20 mL) to give compound 1, 42.2 mg (78.0% yield).% yield). ¹HNMR (400 MHz, d4-MeOH): δ 8.50 (s, 1H), 8.20 (s, 1H), 8.11 (s, 1H), 7.58(m, 6H), 4.67(s, 2H), 3.73 (m, 1H), 3.45 (m, 3H), 3.18 (m, 1H), 2.38 (m,1H), 2.00 (m, 3H); MS (EI) for C₂₅H₂₅N₈OCl: 489.24 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-chlorobenzamide:1H NMR (400 MHz, d4-MeOH): δ 8.52 (s, 1H), 8.14 (s, 1H), 8.00 (d, 1H),7.84 (d, 2H), 7.42 (m, 4H), 4.62(s, 2H), 3.65 (m, 2H), 3.42 (m, 2H),3.16 (m, 1H), 2.38 (m, 1H), 2.00 (m, 3H); MS (EI) for C₂₅H₂₅N₈OCl:489.20 (MH⁺).

N-([3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl)phenyl]methyl}-4-iodobenzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.58 (s, 1H), 8.18 (s, 1H), 7.98 (d, 1H),7.81 (d, 2H), 7.62 (m, 2H), 7.40 (m, 2H), 4.62(s, 2H), 3.64 (m, 2H),3.42 (m, 2H), 3.17 (m, 1H), 2.38 (m, 1H), 2.00 (m, 3H); MS (EI) forC₂₅H₂₅N₈OI: 581.16 (MH⁺).

N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-3,5-difluorobenzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.55 (s, 1H), 8.18 (s, 1H), 7.98 (d, 1H),7.42 (m, 4H), 7.18 (m, 1H), 4.62(s, 2H), 3.70 (m, 2H), 3.42 (m, 2H),3.17 (m, 1H), 2.38 (m, 1H), 2.00 (m, 3H); MS (EI) for C₂₅H₂₄N₈OF₂:491.21 (MH⁺).

N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-yl)phenyl]methyl}-4-bromo-2-fluorobenzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.50 (s, 1H), 8.18 (s, 1H), 8.00 (d, 1H),7.62 (t, 1H), 7.42 (m, 4H), 4.62(s, 2H), 3.63 (m, 2H), 3.42 (m, 2H),3.17 (m, 1H), 2.38 (m, 1H), 2.00 (m, 3H); MS (EI) for C₂₅H₂₄N₈OFBr:553.16 (M+2).

N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-11-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}4-bromo-2-chlorobenzamide:¹H NMR (400 MHz, d4-MeOH): δ 8.50 (s, 1H), 8.18 (s, 1H), 8.00 (d, 1H),7.62 (s, 1H), 7.42 (m, 4H), 4.62(s, 2H), 3.63 (m, 2H), 3.42 (m, 2H),3.17 (m, 1H), 2.38 (m, 1H), 2.00 (m, 3H); MS (EI) for C₂₅H₂₄N₈OClBr:567.14 (M⁺).

3-amino-6-{3-[({[(4-chlorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.42 (s, 1H), 9.30 (m, 1H), 9.12 (m, 1H),8.71 (d, 1H), 8.15 (s, 1H), 8.00 (d, 1H), 7.42 (m, 3H), 7.38 (m, 3H),4.80(br, 2H), 4.40 (s, 2H), 4.35 (m, 1H), 3.60 (m, 1H), 3.20 (m, 3H),2.72 (m, 1H), 1.80 (m, 4H); MS (EI) for C₂₄H₂₆N₇O₂Cl: 480.19 (MH⁺).

Example 61

Scheme 24 depicts synthesis of amides of the invention according toformula I, from corresponding esters. In general, esters, for examplepyrazine ester (ci), are combined with amines, for example as depicted,to give amides, for example (cii), according to formula I.

3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide

A mixture of3-amino-6-{3-[(2-hydroxy-indan-1-ylamino)-methyl]-phenyl}-pyrazine-2-carboxylicacid methyl ester (400.0 mg, 1.02 mmol) and 1,1-dimethylethyl(3S)-3-aminopiperidine-1-carboxylate (970.0 mg, 4.84 mmol) was heated to120° C. overnight. The reaction mixture was poured into water (100 mL),and extracted with ethyl acetate (2×50 mL) then dried over anhydroussodium sulfate and filteration, concentration and purified by columnchromatography (3% MeOH/Dichloromethane) and subsequently it was treatedwith 4.0 M HCl in dioxane (20 mL) to give3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide,275.0 mg (58.7% yield). ¹H NMR (400 MHz, d4-MeOH): δ 8.72 (s, 2H), 8.18(s, 1H), 7.80 (d, 1H), 7.60 (m, 2H), 7.38 (m, 3H), 4.80 (s, 1H), 4.50(s,2H), 4.40 (m, 1H), 3.65 (m, 2H), 3.42 (m, 5H), 3.16 (m, 2H), 2.15 (m,2H), 1.87 (m, 1H); MS (EI) for C₂₆H₃₀N₆O₂: 459.31 (MH⁺).

Example 623-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide

To a solution of3-amino-N-ethyl-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carboxamide (566.1mg, 1.0 eq) in dichloromethane (20 mL) were added carbon tetrabromide(749.8 mg, 1.1 eq), triphenylphosphine (600 mg, 1.1 eq) at ambienttemperature. After being stirred for 7 h, the reaction mixture waspartitioned with dichloromethane (10 mL×3), washed with brine. Theorganic layer was combined and dried over anhydrous magnesium sulfate.Filteration and concentration in vacuo gave a crude product.Purification by column chromatography afforded the3-amino-6-[3-(bromomethyl)phenyl]-N-ethylpyrazine-2-carboxamide (534 mg,77% yield): ¹H NMR (400 MHz, DMSO-d6): δ 8.87 (m, 2H), 8.84 (s, 2H),8.23 (m, 1H), 7.61 (bs, 1H), 7.45 (m, 1H), 4.77 (s, 2H), 3.38 (m, 2H),1.16 (m, 3H).

The 3-amino-6-[3-(bromomethyl)phenyl]-N-ethylpyrazine-2-carboxamide (112mg, 1.0 eq) was dissolved in acetonitrile (5 mL) and treated with(1S)-2,3-dihydro-1H-inden-1-amine (133.8 mg, 3.0 eq),diisopropylethylamine (69.3 mg, 1.6 eq) at ambient temperature. Afterbeing stirred for 7 h, the white suspension was filtered on Celite andconcentrated in vacuo. The resulting residue was purified by flashcolumn chromatography to give the3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide(50.2 mg, 39% yield): ¹H NMR (400 MHz, CD₃OD): δ 8.72 (s, 1H), 8.21 (s,1H), 8.11 (d, 1H), 7.61 (d, 1H), 7.58 (t, 1H), 7.49 (d, 1H), 7.39 (d,2H), 7.39 (d, 2H), 7.37 (m, 1H), 4.38 (s, 2H), 3.47 (m 1H), 3.23 (m,1H), 3.01 (m, 1H), 2.64 (m, 1H), 2.39 (m, 1H); MS (EI) for C₂₃H₂₅N₅O:388.22 (MH⁺).

3-Amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide:The 3-Amino-6-[3-(bromomethyl)phenyl]-N-ethylpyrazine-2-carboxamide (100mg, 1.0 eq) was dissolved in acetonitrile (5 mL) and treated with[(1S)-5,7-difluoro-2,3-dihydro-1H-inden-1-yl]amine (151 mg, 3.0 eq),diisopropylethylamine (62 mg, 1.6 eq) at ambient temperature. Afterbeing stirred for 8 h, the white suspension was concentrated in vacuoand purified by flash column chromatography to give the title compoundas colorless oil, which was dissolved in ethyl acetate (10 mL) andtreated 1M HCl in ether. The resulting precipitate was filtered, washedwith ether (2×2mL), and dried to afford 42mg (12% yield) of3-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-ethylpyrazine-2-carboxamidehydrochloride as a yellow solid: ¹H NMR (400 MHz, CD₃OD): δ 8.71 (s,1H), 8.22 (s, 1H), 8.13 (d, 1H), 7.57 (t, 1H), 7.51 (m, 1H), 7.06 (m,1H), 6.98 (m, 1H), 5.08 (m, 1H), 4.38 (q, 2H), 3.45 (m, 2H), 3.39 (m,1H), 3.05 (m, 1H), 2.84 (m, 1H), 2.53 (m, 1H); MS (FI) for C₂₃H₂₃NSOF₂:424.16 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(naphthalen-2-ylmethyl)pyrazine-2-carboxamide:To a solution of methyl3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylaminomethyl}phenyl)pyrazine-2-carboxylate(1.0 eq) in methyl alcohol was added 2-aminonaphthalene (10.0 eq) andthe reaction mixture was allowed to heat at 85° C. overnight. Thesolvent was removed followed by preparative HPLC (0.1% TFA in water/0.1%TFA in CH₃CN), which was neutralized by aqueous saturated sodiumbicarbonate solution and partitioned with ethyl acetate. The aqueousphase was extracted once with additional ethyl acetate. The combinedorganic layers were washed with saturated aqueous sodium chloride thendried over anhydrous magnesium sulfate. Filtration and concentration toca. 1 mL followed by addition of 1.0 M HCl in ether. The resultingprecipitate was filtered and dried to give3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(naphthalen-2-ylmethyl)pyrazine-2-carboxamidehydrochloride as a yellow solid: ¹H NMR (400 MHz, CD₃OD): δ 8.66 (s,1H), 8.10 (d, 1H), 8.01 (m, 2H), 7.82 (d, 1H), 7.78 (d, 1H), 7.44 (m,4H), 7.39 (m, 2H), 7.30 (m, 2H), 7.21 (m, 1H), 5.04 (s, 2H), 4.79 (m,1H), 4.21 (s, 2H), 3.12 (m, 1H), 2.90 (m, 1H), 2.51 (m, 1H), 2.20 (m,1H); MS (EI) for C₃₂H₂₉N₅O: 501.17 (MH⁺).

3-Amino-N-cyclohexyl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.70 (s, 1H), 8.11 (m, 2H), 7.62 (m, 2H),7.53 (m, 1H), 7.41 (m, 2H), 7.33 (m, 1H), 4.40 (s, 2H), 3.93 (m, 1H),3.15 (m, 1H), 2.75 (m, 1H), 2.41 (m, 1H), 2.00 (m, 2H), 1.84 (m, 2H),1.75 (m, 1H), 1.50 (m, 2H); MS (EI) for C₂₇H₃₁N₅O: 442.24 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(pyridin-4-ylmethyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.78 (m, 3H), 8.70 (m, 1H), 8.14 (m, 3H),7.74 (d, 1H), 7.57 (t, 1H), 7.50 (m, 1H), 7.38 (m, 2H), 7.22 (m, 1H),4.92 (s, 2H), 4.40 (s, 2H), 3.21 (m, 1H), 3.00 (m, 1H), 2.61 (m, 1H),2.42 (m, 1H); MS (EI) for C₂₇H₃₁N₅O: 451.12 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-pyrrolidin-1-ylethyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.83 (s, 1H), 8.78 (s, 1H), 8.15 (d, 1H),7.91 (d, 1H), 7.56 (m, 2H), 7.41 (m, 2H), 7.38 (m, 1H), 4.41 (s, 2H),3.82 (m, 4H), 3.54 (m, 2H), 3.24 (m, 1H), 3.18 (m, 1H), 3.05 (m, 1H),2.83 (m, 1H) 2.43 (m, 1H), 2.17 (m, 2H), 2.10 (m, 2H); MS (EI) forC₂₇H₃₂N₆O: 457.21 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-piperidin-1-ylethyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.88 (t, 1H), 8.76 (s, 1H), 8.09 (m, 1H),7.79 (d, 1H), 7.54 (m, 2H), 7.38 (m, 2H), 7.31 (m, 1H), 4.92 (m, 1H),4.42 (s, 1H), 4.4-3.8 (m, 4H), 3.83 (t, 1H), 3.72 (d, 1H), 3.44 (t, 1H),3.40 (m,1H), 3.05 (m, 2H), 2.66 (m, 1H), 2.52 (m, 1H), 1.80 (m, 4H),1.49 (m, 1); MS (EI) for C₂₈H₃₄N₆O: 471.20 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-morpholin-4-ylethyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.90 (s, 1H), 8.75 (s, 1H), 8.08 (m, 1H),7.78 (d, 1H), 7.57 (d, 2H), 7.38 (m, 2H), 7.32 (m, 1H), 4.43 (s, 2H),4.25 (m, 3H), 3.94 (t, 2H), 3.87 (m, 2H), 3.77 (m, 2H), 3.57 (t, 2H),3.32 (m, 2H), 3.04 (m, 1H), 2.66 (m, 1H), 2.51 (m, 1H); MS (EI) forC₂₇H₃₂N₆O₂: 471.20 (MH⁺).

3-amino-N-(cyclopropylmethyl)-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino}methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.58 (s, 1H), 8.13 (t, 1H), 7.91 (s, 1H),7.72 (m, 1H), 7.40 (m, 3H), 7.17 (m, 2H), 4.32 (t, 1H), 3.45 (s, 2H),3.33 (t, 2H), 3.02 (m, 1H), 2.72 (m, 1H), 2.46 (m, 1H1), 1.90 (m, 1H),1.20 (m, 2H), 0.55 (m, 2H), 0.37 (m, 2H); MS (EI) for C₂₅H₂₇N₅O: 414.21(MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(phenylmethyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,CD₃OD): δ 8.70 (s, 1H), 8.39 (m, 1H), 8.14 (m, 1H), 7.66 (d, 1H), 7.54(t, 1H), 7.52 (m, 1H), 7.40 (m, 3H), 7.11 (m, 1H), 7.24 (m, 1H), 4.66(s, 2H), 4.39 (s, 2H), 3.23 (m, 1H), 3.02 (m, 1H), 2.61 (m, 1H), 2.41(m, 1H); MS (EI) for C₂₈H₂₇N₅O: 451.20 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-phenylethyl)pyrazine-2-carboxamide: ¹H NMR (400 MHz,CD₃OD): δ 8.68 (s, 1H0, 8.35 (m, 1H), 8.08 (m, 1H), 7.69 (d, 1H), 7.57(m, 2H), 7.40 (m, 1H), 7.32 (m, 6H), 7.21 (m, 1H), 4.95 (m, 1H), 4.39(s, 2H), 3.64 (q, 2H), 3.23 (m, 1H), 3.06 (m, 1H1), 3.92 (t, 2H), 2.65(m, 1H), 2.42 (m, 1H); MS (EI) for C₂₉H₂₉N₅O: 464.20 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(dimethylamino)ethyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.708 (s, 1H), 8.74 (m, 1H), 8.13 (m, 1H),7.58 (d, 1H), 7.59 (t, 1H), 7.48 (m, 1H), 7.40 (m, 2H), 7.35 (m, 1H),4.40 (s, 2H), 3.78 (t, 2H), 3.50 (t, 2H), 3.59 (m, 1H), 3.02 (m, 7H),2.65 (m, 1H), 2.45 (m, 1H); MS (EI) for C₂₅H₃₀N₆O: 431.22 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide: ¹H NMR(400 MHz, CD₃OD): δ 8.81 (s, 1H), 8.65 (s, 1H), 8.63 (s, 1H), 8.10 (d,1H), 7.73 (d, 1H), 7.56 (m, 2H), 7.41 (m, 2H), 7.38 (m, 1H), 4.41 (m,2H), 3.80 (t, 2H), 3.28 (m, 1H), 3.17 (t, 2H), 3.04 (m, 1I1), 2.65 (m,1H) 2.57 (m, 1H), 2.17 (m, 2H); MS (EI) for C₂₆H₂₇N₇O: 454.18 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(methylamino)ethyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.80 (s, 1H), 8.78 (s, 1H), 8.12 (d, 1H),7.79 (d, 1H), 7.57 (m, 2H1), 7.39 (m, 2H), 7.33 (m, 1H), 4.40 (s, 2H),3.82 (t, 2H), 3.27 (m, 1H), 3.17 (t, 21), 3.02 (m, 1H), 2.67 (m, 1H)2.43 (m, 1H); MS (EI) for C₂₄H₂₈N₆O: 417.21 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(dimethylamino)propyl]pyrazine-2-carboxamide: ¹H NMR (400MHz, CD₃OD): δ 8.80 (s, 1H), 8.72 (s, 1H), 8.11 (d, 1H), 7.79 (d, 1H),7.58 (m, 2H), 7.39 (m, 2H), 7.32 (m, 1H), 4.40 (s, 2H), 3.61 (t, 2H),3.52 (m, 5H), 3.05 (m, 1H), 2.71 (m, 1H) 2.49 (m, 1H), 2.12 (m, 2H); MS(E) for C₂₆H₃₂N₆O: 445.21 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(1H-imidazol-1-yl)propyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 9.10 (s, 1H), 8.68 (s, 1H), 8.03 (d, 2H),7.51 (m, 2H), 7.46 (m, 3H), 7.30.(d, 1H), 7.22 (m, 2H), 4.31 (m, 4H),3.48 (t, 2H), 3.41 (m, 1H), 2.93 (m, 1H), 2.52 (m, 1H) 2.38 (m, 1H),2.23 (m, 1H); MS (EI) for C₂₇H₂₉N₇O: 468.18 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(methylamino)propyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.64 (s, 1H), 8.63 (s, 1H), 8.02 (d, 1H),7.43 (m, 2H), 7.31 (m, 2H), 7.22 (m, 1H), 4.85 (m, 1H), 4.31 (s, 2H),3.50 (t, 2H), 3.18 (m, 1H), 2.95 (m, 311), 2.62 (s, 2H) 2.53 (m, 1H),2.37 (m, 1H), 1.98 (m, 1H); MS (EI) for C₂₅H₃₀N₆O: 431.22 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-pyrrolidin-1-ylpropyl)pyrazine-2-carboxamide: ¹H NMR (400MHz, CD₃OD): δ 8.83 (s, 1H), 8.73 (s, 1H), 8.10 (d, 1H), 7.79 (d, 1H),7.59 (m, 211), 7.38 (m, 2H), 7.32 (m, 1H), 4.43 (s, 2H), 3.67 (m, 4H),3.20 (m, 4H), 2.63 (m, 2H) 2.48 (m, 1H), 2.14 (m, 1H), 2.02 (m, 2H); MS(EI) for C₂₈H₃₄N₆O: 471.22 (MH⁺).

3-Amino-N-1-azabicyclo[2.2.0]oct-3-yl-6-(3-{[(1S)-2,3-dihydro-ylamino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.77 (s, 1H), 8.45 (m, 1H), 8.12 (d, 1H),7.52 (d, 1H), 7.56 (t, 2H), 7.49 (d, 1H), 7.40 (d, 2H), 7.35 (m, 1H),4.55 (m, 1H), 4.40 (s, 2H), 3.79 (d, 2H), 3.63 (d, 1H), 3.03 (m, 1H),2.68 (m, 1H), 2.43 (m, 2H) 2.31 (m, 1H), 2.15 (m, 2H), 2.31 (m, 1H),2.15 (m, 2H), 1.83 (m, 1H); MS (EI) for C₂₈H₃₂N₆O: 469.13 (MH⁺).

3-Amino-N-[(3R)1-azabicyclo[2.2.0]oct-3-yl]-6-(3-{[(1S)-2,3-dihyddro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 10.22 (bs, 1H), 10.10 (m, 1H), 9.95 (m,1H), 9.08 (d, 1H), 8.93 (s, 2H), 8.12 (m, 1H), 7.91 (d, 1H), 7.70 (bs,2H), 7.50 (d, 2H), 7.37 (d, 2H), 7.31 (m, 1H), 4.82 (bs, 1H), 4.49 (m,1H), 4.38 (t, 2H), 4.02 (m, 1H), 3.60 (t, 1H), 3.21 (m, 4H), 2.90 (m,1H), 2.44 (m, 2H), 2.13 (m, 1H), 1.94 (m, 2H), 1.73 (m, 1H); MS (EI) forC₂₈H₃₂N₆O: 469.15 (MH⁺).

3-Amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.94 (bs, 2H), 9.58 (bs, 1H), 9.33 (bs,1H), 9.10 (d, 1H), 8.91 (m, 2H), 8.09 (m, 1H), 7.88 (m, 1H), 7.47 (m,2H), 7.42 (m, 2H), 7.27 (m, 2H), 4.82 (m, 1H), 4.49 (m, 1H), 4.36 (m,2H), 3.48 (m, 1H), 3.30 (m, 3H), 3.05 (m, 1H), 2.82 (m, 1H), 2.48 (m,2H), 2.10 (m, 1H), 2.00 (m, 1H), 1.85 (m, 3H), 1.62 (m, 1H) MS (EI) forC₂₇H₃₂N₆O: 457.12 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carbohydrazide:¹H NMR (400 MHz, d₆-DMSO): 9.96 (m, 1H), 8.80 (s, 1H), 8.16 (s, 1H),8.01 (d, 1H), 7.56 (br s, 2H), 7.38 (m, 3H), 7.19 (m, 1H1), 7.15 (m,2H), 4.57 (d, 2H), 4.16 (m, 1H), 3.86 (m, 2H), 2.92 (m, 1H), 2.72 (m,1H), 2.53 (m, 1H), 2.31 (m, 1H), 1.81 (m, 1H); MS (EI) for C₂₁H₂₂N₆O:375.2 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(5-hydroxypentyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.59 (s, 1H), 8.18 (t, 1H), 7.95 (s, 1H), 7.70(d, 1H), 7.39 (m, 3H), 7.21 (m, 3H), 4.35 (t, 1H), 3.98 (m, 2H), 3.60(m, 2H), 3.47 (m, 2H), 3.03 (m, 1H), 2.84 (m, 1H), 2.47 (m, 1H), 2.04(br s, 3H), 1.93 (m, 1H), 1.68 (m, 2H), 1.60 (m, 2H), 1.51 (m, 2H); MS(EI) for C₂₆H₃₁N₅O₂: 446.2 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylaminomethyl}phenyl)-N-(4-hydroxybutyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.84 (m, 1H), 8.60 (s, 1H), 8.23 (s, 1H), 7.69(d, 1H), 7.36 (m, 2H), 7.28 (m, 1H1), 7.24 (m, 1H), 7.21 (m, 2H), 4.37(t, 1H), 3.96 (m, 2H), 3.47 (m, 4H), 3.05 (m, 1H), 2.85 (m, 1H), 2.63(br s, 2H), 2.46 (m, 1H), 1.98 (m, 1H), 1.76 (m, 2H), 1.63 (m, 2H); MS(E1) for C₂₅H₂₉N₅O₂: 432.2 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N′-methylpyrazine-2-carbohydrazide:¹H NMR (400 MHz, CDCl₃): 9.24 (s, 1H), 8.66 (s, 1H), 7.91 (s, 1H), 7.74(m, 1H), 7.44 (m, 2H), 7.41 (m, 1H), 7.25 (m, 1h), 7.22 (m, 2H), 4.35(t, 1H), 4.00 (m, 2H), 3.05 (m, 1H), 2.85 (m, 1H), 2.77 (s, 3H), 2.48(m, 1H), 1.93 (m, 1H); MS (EI) for C₂₂H₂₄N₆O: 389.2 (MH⁺).

3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N,N-dimethylpyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): 8.51 (s, 1H), 7.89 (s, 1H), 7.74 (m, 1H), 7.40(m, 3H), 7.22 (m, 3H), 5.86 (br s, 211), 4.32 (t, 1H), 3.98 (m, 2H),3.31 (s, 3H), 3.17 (s, 3H), 3.03 (m, 1H), 2.83 (m, 1H), 2.45 (m, 1H),1.91 (m, 1H); MS EI) for C₂₃H₂₅N₅O: 388.2 (MH⁺).

Example 63 Synthesis of Compounds According to Formula I, Wherein A is—(C═O)— or —(C═NR⁶)— Derived from methyl 3-amino-2-pyrazine carboxylate

Methyl 3-amino-6-bromopyrazine-2-carboxylate. To a solution of methyl3-amino-2-pyrazine carboxylate (30.0 g, 200 mmol) in acetic acid (200mL), bromine (11 mL) was added slowly via addition funnel. Aftercomplete addition of bromine, sodium carbonate powder was added slowlyuntil precipitation occurred. The reaction mixture was allowed to stirat room temperature for 2 h. The reaction mixture was reduced tohalf-volume in vacuo and then diluted with water (500 mL). The reactionmixture was shaken vigorously and the resulting solid was collectedusing vacuum filtration. The solid was washed with ether to afford apure yellow solid (91% yield).

3-Amino-6-bromopyrazine-2-carboxylic acid. To a solution ofmethyl-3-amino-6-bromopyrazine carboxylate (10 g, 43 mmol) in THF:H₂O(3:1), lithium hydroxide (6.0 g, 140 mmol) was added. The reactionmixture was stirred at room temperature and monitored by LCMS. Thereaction was complete after 1 h. The reaction mixture was poured into 1N HCl (250 mL), extracted with ethyl acetate (3×, 200 mL), washed withbrine (3×, 100 mL), dried over anhydrous sodium sulfate, filtered andconcentrated to afford a yellow solid (100% yield).

3-Amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:To a solution of 3-amino-6-bromopyrazine-2-carboxylic acid (4.0 g, 18mmol) in DMF, HATU (10.4 g, 27.5 mmol), N,N-diisopropylethylamine (8.5mL, 27.5 mmol) and (S)-3-amino-1-N-Boc-piperidine (4.0 g, 20 mmol,commercially available from Astatech and Arch Corporation) were added.The reaction was allowed to stir at room temperature for 1 h. Thereaction mixture was diluted with water (100 mL), extracted with ethylacetate (3×, 200 mL), washed with 5% LiCl (3×, 100 mL) and brine (3×,100 mL), dried over anhydrous sodium sulfate, filtered and concentratedin vacuo to afford a brown solid (MS (ESI-LCMS) for C₁₅H₂₂BrN₅O₃: 400(MH⁺). This material was taken up in ethylene glycol dimethyl ether (150mL), and triethylamine (4.6 mL, 45 mmol), Pd(dppf)₂Cl₂ (2.3 g, 2.75mmol), 3-carboxyphenylboronic acid (3.6 g, 21.8 mmol) and water (15 mL)were added. The reaction was refluxed at 85° C. and monitored by LCMS.The reaction was complete after 3 h. The solvent was removed underreduced pressure to afford a brown solid. The crude product was purifiedby silica gel chromatography to afford a yellow solid (MS (ESI-LCMS) forC₂₂H₂₇N₅O₅: 442 (MH⁺). A portion of this intermediate (50 mg, 0.11 mmol)was dissolved in DMF (1 mL), and HATU (62.7 mg, 0.165 mmol),N,N-diisopropylethylamine (29 μL, 0.16 mmol) and 2-phenylbenzylamine(24.2 mg, 0.132 mmol) were added. The reaction was stirred at roomtemperature and monitored by LCMS. The reaction was complete after 1 h.The crude product was purified by preparative HPLC and lyophilized toafford a white solid (MS (ESI-LCMS) for C₃₅H₃₈N₆O₄: 607 (MH⁺). Thismaterial was dissolved in methanol (2 mL), and 4M HCl in dioxane (2 mL)was added. The reaction was stirred at room temperature and monitored byLCMS. The reaction was complete after 1 h. The solvents were removedunder reduced pressure to afford a yellow gel product. The yellow gelproduct was dissolved in acetonitrile-water (2 mL), frozen andlyophilized to afford a yellow solid: ¹H NMR (400 MHz, d₆-DMSO): δ 9.25(t, 1H), 9.05 (d, 1H), 8.95 (s, 1H), 8.9 (d, 1H), 8.85 (d, 1H), 8.6 (s,1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.5-7.3 (m, 8H), 7.25 (m,1H), 4.5 (d, 2H), 4.35 (m, 1H), 3.25 (m, 2H), 3.05 (m, 1H), 2.75 (m,1H), 1.95-1.7 (m, 4H). MS (EI) for C₃₀H₃₀N₆O₂: 507 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:To a solution of 3-carboxyphenyl boronic acid (20.0 g, 120 mmol) inthionyl chloride (120 mL) was added DMF (3 drops). The reaction mixturewas allowed to stir at room temperature overnight. Excess thionylchloride was removed under reduced pressure to afford a white solid. Toa solution of this residue and triethylamine (33.4 mL, 240 mmol) in TBF(200 mL) at 0° C. was added slowly (S)-(+)-1-aminoindane (19.2 g, 144mmol) in MeOH (100 mL) via addition funnel. After addition of(S)-(+)-1-aminoindane, the reaction mixture was stirred at roomtemperature and monitored by LCMS. The reaction was complete after 3 h.The reaction mixture was then concentrated under reduced pressure toafford a white solid. This material (33.72 g, 120 mmol) was added to asolution of methyl-3-amino-6-bromopyrazine carboxylate (23.2 g, 100mmol) in DMF (200 mL), and triethylamine (28 mL, 200 mmol), Pd(dppf)₂Cl₂(8.16 g, 10 mmol) and water (20 mL) were added. The reaction mixture wasstirred at 80° C. overnight. The reaction mixture was cooled to roomtemperature. Water (800 mL) was added and the precipitated solid wascollected via vacuum filtration and subsequently washed with water andether. The desired product (80% pure) was carried to the next stepwithout further purification (MS (ESI-LCMS) for C₂₂H₁₉N₃O₃: 375.2 (MH⁺).To a solution of this material in TBF:H₂O (3:1), was added lithiumhydroxide (13.85 g, 330 mmol). The reaction was stirred at roomtemperature and monitored by LCMS. The reaction was complete after 3 h.The reaction mixture was poured into 1N HCl (500 mL) and shakenvigorously. Vacuum filtration was used to collect the resulting yellowsolid, which was confirmed by LCMS. Extraction of the aqueous layer withethyl acetate (3×, 1L) was used to recover the remaining product. Thecombined organic layers were washed with brine (3×, 200 mL), dried overanhydrous sodium sulfate, filtered and concentrated in vacuo to afford ayellow solid (MS (ESI-LCMS) for C₂₁H₁₇N₃O₃: 360.2 (MH⁺). To a portion ofthis yellow solid (2.0 g, 5.4 mmol) in DMF (50 mL) was added HATU (3.1g, 8.1 mmol), N,N-diisopropylethylamine (2.8 mL, 16 mmol) and(S)-3-amino-1-N-Boc-pyrrolidine (1.5 g, 8.1 mmol). The reaction mixturewas stirred at room temperature and monitored by LCMS. The reaction wascomplete after 1 h. The reaction mixture was diluted with water (200mL), extracted with ethyl acetate (3×, 300 mL), washed with 5% LiCl (3×,100 mL) and brine (3×, 200 mL), dried over anhydrous sodium sulfate,filtered and concentrated under reduced pressure. The material waspurified by silica gel chromatography to afford a yellow solid (2.2 g,92% yield) (MS (ESI-LCMS) for C₃₀H₃₄N₆O₃₄: 443.2 (MH⁺). This materialwas dissolved in methanol (10 mL), and 4M HCl in dioxane (10 mL) wasadded. The reaction mixture was stirred at room temperature andmonitored by LCMS. The reaction was complete after 2 h. The reactionmixture was concentrated in vacuo to afford a yellow solid as an HClsalt. ¹H NMR (400 MHz, d₆-DMSO): δ 9.1 (d, 1H), 8.95 (s, 1H), 8.75 (d,1H), 8.65 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.3-7.2 (m,4H), 5.6 (q, 1H), 4.4 (m, 1H), 3.1-2.8 (m, 6H), 2.0 (m, 2H), 1.7 (m,2H), 1.85 (m, 2H). MS (EI) for C₂₅H₂₆N₆O₂: 443 (MH⁺).

3-Amino-6-{3-[(benzylamino)carbonyl]phenyl}-N-methoxy-N-methylpyrazine-2-carboxamide:3-Carboxyphenylboronic acid (10 g, 61 mmol) was dissolved in thionylchloride (60 mL) and DMF (catalytic), and the mixture was stirred atroom temperature for 12 h. Thionyl chloride and DMF were removed underreduced pressure and the acid chloride was isolated as a white solid. ATHF (100 mL) solution of the acid chloride was added dropwise to a MeOH(100 mL) solution of benzylamine (7 mL, 64 mmol) and triethylamine (18mL), and the mixture was stirred at room temperature for 2 h. Thesolvent was removed under reduced pressure to give the benzamide as awhite solid (MS (EI) for C₁₄H₁₄BN₂O₃: 256 (MH⁺). A mixture containingthis benzamide (15 g, 59 mmol), methyl-3-amino-6-bromopyrazinecarboxylate (15 g, 66 mmol), tris(dibenzylideneactone)dipalladium (1.4g, 1.5 mmol), 1,1′-bis(diphenylphosphine) ferrocene (1.0 g, 1.9 mmol),and triethylamine (100 mL, 720 mmol) in DMF (200 mL) and water (30 mL),was heated at 80° C. for 48 h. The reaction mixture was cooled to roomtemperature and diluted with water and ethyl acetate. The layers wereseparated and the organic layer was extracted 2× with 5% aqueous lithiumchloride, dried over sodium sulfate, filtered, and concentrated underreduced pressure to give a brown solid. The product was purified bytriturating the brown solid with dichloromethane (100 mL) and filteringthe resultant mixture to give the methyl ester as a yellow solid (3.0 g,15% yield). N,O-Dimethylyhdroxylamine was dissolved in anhydrousdichloromethane (15 mL). Trimethylaluminum (7 mL of a 2.0 M solution inhexanes) was added dropwise at 0° C. under N₂ and the solution waswarmed to room temperature and stirred for 30 min. The previouslyprepared methyl ester (1.0 g, 2.8 mmol) was stirred in anhydrousdichloromethane (40 mL) and this solution was added in small portions tothe reaction under N₂. The resulting solution was stirred at roomtemperature for 12 h. The reaction mixture was acidified with 0.5 Naqueous hydrochloric acid and extracted 3× with dichloromethane. Thecombined organic layers were washed with brine, dried over sodiumsulfate, filtered, and concentrated under reduced pressure to give theproduct as a yellow solid (0.82 g, 76% yield). ¹H NMR (400 MHz,d₆-DMSO): δ 9.23 (t, 1H), 8.50 (s, 1H), 8.16 (d, 1H), 7.93 (d, 1H), 7.62(t, 1H), 7.43-7.38 (m, 5M), 7.35-7.30 (m, 1H), 6.82 (br s, 2H), 4.58 (d,2H), 3.76 (s, 3H), 3.40 (s, 3H). MS (EI) for C₂₀H₂₁N₅O₃: 392 (MH⁺).

3-{5-Amino-6-[(3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:3-Fluorophenylmagnesium bromide (1.5 mL of a 0.5 M solution in TBF, 0.75mmol) was added dropwise to a THF (10 mL) solution of3-amino-6-{3-[(benzylamino)carbonyl]phenyl}-N-methoxy-N-methylpyrazine-2-carboxamide(0.10 g, 0.25 mmol) at 0° C. under N₂. The reaction mixture was warmedto room temperature and stirred for 2 h. The mixture was diluted withwater and extracted 3× with ethyl acetate. The combined organic layerswere dried with magnesium sulfate, filtered, and concentrated underreduced pressure to give a yellow oil. The crude product was separatedby preparative HPLC and lyophilized to give a yellow solid (4 mg, 4%yield). ¹H NMR (400 MHz, d₆-DMSO): δ 9.10 (t, 1H), 9.05 (s, 1H), 8.42(bs, 1H), 8.01 (m, 2H), 7.86-7.80 (m, 2H), 7.74 (d, 1H), 7.57-7.51 (m,2H), 7.47-7.43 (m, 2H), 7.38-7.32 (m, 2H), 7.28-7.24 (m, 2H), 6.47-6.59(m, 1H), 4.50 (d, 2H). MS (EI) for C₂₅H₁₉FN₄O₂: 427 (MH⁺).

3-(5-Amino-6-{(1E)-N-[4-(methyloxy)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:A solution of3-amino-6-{3-[(benzylamino)carbonyl]phenyl}-N-methoxy-N-methylpyrazine-2-carboxamide(0.10 g, 0.25 mmol) in THF (5 mL) was cooled to 0° C., and a solution ofCH₃MgCl (0.75 mL, 1 M in THF, 3.0 equiv.) was added slowly. The mixturewas allowed to warm to room temperature over 1.5 hr. The mixture wasthen cooled to 0° C. and quenched slowly with saturated NH₄Cl solution.The mixture was extracted with ethyl acetate, washed with brine thenwater. The ethyl acetate extract was evaporated to afford thecorresponding methyl ketone as a yellow solid. To a portion of thisresidue (35 mg, 0.1 mmol) in ethanol in a pressure tube (5 mL) was added4-methoxyphenylhydrazine hydrochloride (52 mg, 3 mmol). This mixture wasthen heated to for 12 h. The solvent was removed under reduced pressureand the crude mixture was dissolved in a minimal amount of methanol andrun through a plug of silica gel to give the product as a white solid(33 mg, 70% yield). ¹H NMR (400 MHz, CDCl₃): δ 8.40 (m, 1H), 8.0 (m,2H), 7.80 (m, 2H), 7.25 (m,1H), 7.2 (m, 4H), 6.9 (m, 4H), 4.8 (s, 2H),3.8 (s, 3H), 2.6 (s, 3H). MS (EI) for C₂₇H₂₆N₆O₂: 467 (MH⁺).

3-(5-Amino-6-formylpyrazin-2-yl)-N-benzylbenzamide: A solution of3-amino-6-{3-[(benzylamino)carbonyl]phenyl}-N-methoxy-N-methylpyrazine-2-carboxamide(2.5 g, 6.4 mmol) in THF (20 mL) was cooled to 0° C. Under N₂ lithiumaluminum hydride (0.364g, 9.58 mmol) was added and the reaction wasstirred at 0° C. for 1 h. The mixture was then quenched with H₂O at 0°C. Removal of solids via filtration, concentration of the filtrate anddissolution of the solid residue in H₂O followed by washing 3× withdichloromethane gave the product (1.90 g, 89% yield) with sufficientpurity to be used without further purification.

3-[5-Amino-6-(morpholin-4-ylmethyl)pyrazin-2-yl]-N-(phenylmethyl)benzamiide:3-(5-Amino-6-formylpyrazin-2-yl)-N-benzylbenzamide (1.27 g, 3.83 mmol)was dissolved in dichloroethane (30 mL) at 0° C. Morpholine (400 mg, 4.6mmol), and NaBH(OAc)₃ (2.03 g, 9.58 mmol) were added and the reactionwas stirred at room temperature for 20 h. The reaction mixture wasdiluted with saturated sodium carbonate and extracted 3× with ethylacetate. The combined ethyl acetate layers were dried over sodiumsulfate, filtered, and concentrated iii vacuo to afford the product(1.41 g, 88% yield). ¹H NMR (400 MHz, d₄-CD₃OD): δ 8.60 (s, 1H), 8.47(t, 1H), 8.12 (m, 1H), 7.84 (m, 1H), 7.55 (t, 1H), 7.31-7.89 (m, 4H),7.23-7.26 (m, 1H), 4.61 (s, 2H), 4.43 (s, 2H), 3.32-4.16 (m, 8H). MS(EI) for C₂₃H₂₅N₅O₂: 404 (MH⁺).

Using the same or similar synthetic techniques, substituting with theappropriate reagents such as the respective amines, the followingcompounds of the invention were prepared:

3-{5-Amino-6-[(3,5-difluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.25 (m, 2H), 8.45 (s, 1H), 8.08 (s, 1H),8.05 (m, 1H), 8.02 (m, 1H), 7.67-7.53 (m, 5H), 7.35-7.24 (M, 5H), 4.51(M, 2H). MS (EI) for C₂₅H₁₈F₂N₄O₂: 445 (MH⁺).

3-[5-Amino-6-(biphenyl-4-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.06 (t, 1H), 8.99 (s, 1H), 8.42 (s, 1H),8.06-8.01 (m, 3H), 7.91 (s, 2H), 7.81-7.78 (m, 3H), 7.73-7.71 (m, 2H),7.52-7.44 (m, 3H), 7.40-7.36 (m, 1H), 7.27-7.20 (m, 4H), 7.16-7.12 (m,1H), 4.35 (d, 2H). MS (EI) for C₃₁H₂₄N₄O₂: 485 (MH⁺).

3-{5-Amino-6-[(4-chloro-3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.25 (m, 2H), 8.48 (s, 1H), 8.09 (s, 1H),8.05 (m, 1H), 8.02 (m, 1H), 7.71-7.51 (m, 5H), 7.35-7.24 (m, 5H), 4.51(m, 2H). MS (EI) for C₂₅H₁₉ClFN₄O₂: 461 (MH⁺).

3-(5-Amino-6-{[2,4-bis(methyloxy)phenyl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.11 (m, 1H), 8.95 (s, 1H), 8.36 (s, 1H),7.91-7.83 (m, 4H), 7.53-7.23 (m, 7H), 6.68-6.62 (m, 2H), 4.50 (M, 2H).3.85 (s, 3H), 3.65 (s, 3H). MS (EI) for C₂₇H₂₄N₄O₄: 469 (MH⁺).

3-(5-Amino-6-{[4-(dimethylamino)phenyl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.11 (t, 1H), 8.90 (s, 1H), 8.45 (s, 1H),8.44 (d, 1H), 8.07 (d, 2H), 7.98 (d, 1H), 7.55 (t, 3H), 7.31-7.30 (m,4H), 7.28-7.23 (m, 1H), 6.75 (d, 2H), 4.50 (d, 2H), 3.03 (s, 6H). MS(EI) for C₂₇H₂₅N₅O₂: 452 (MH⁺).

3-{5-Amino-6-[(4-methylphenyl)acetyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d6-DMSO): δ 9.18 (t, 1H), 9.02 (s, 1H), 8.59 (s, 1H),8.26 (d, 1H), 7.91 (d, 2H), 7.61 (t, 1$), 7.38-7.29 (m, 4H), 7.24-7.17(m, 3H), 7.08-7.06 (m, 3H), 4.53-4.51 (m, 4H), 2.23 (s, 3H). MS (EI) forC₂₇H₂₄N₄O₂: 437 (MH⁺).

1,1-Dimethylethyl4-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.16 (t, 1H), 8.9 (s, 1H), 8.55 (d, 1H),8.5 (s, 1H), 8.3 (d, 1H), 7.82 (d, 1H), 7.8-7.6 (m, 1H), 7.57 (t, 1H),7.35-7.2 (m, 5H), 4.5 (d, 2H), 4.0 (m, 3H), 3.0-2.7 (m, 2H), 1.8 (d,2H), 1.6 (q, 2H), 1.4 (s, 9H). MS(EI) for C₂₉H₃₄N₆O₄: 431 (MH⁺).

1,1-Dimethylethyl4-[({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-pyrazin-2-yl]carbonyl}amino)methyl]piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.17 (t, 1H), 8.92 (t, 1H), 8.9 (s, 1H),8.5 (s, 1I1), 8.35 (d, 1H), 7.35 (d, 1H), 7.57 (d, 1H), 7.35-7.2 (m,5H), 4.5 (d, 2H), 3.9 (m, 2H), 3.2 (t, 2H), 2.65 (m, 2H), 1.8-1.6 (m,3H), 1.4 (s, 9H), 1.05 (m, 2H). MS(EI) for C₃₀H₃₆N₆O₄: 445 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-piperidin-4-ylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.3 (t, 1H), 8.9 (s, 1H), 8.8 (d, 1H), 8.65(m, 1H), 8.3 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 4.5(d, 2H), 4.05 (m, 1H), 3.35 (m, 2H), 3.0 (m, 2H), 2.0-1.8 (m, 4H). MS(EI) for C₂₄H₂₆N₆o₂: 431 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-(piperidin-4-ylmethyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d,-DMSO): δ 9.42 (t, 1H), 9.15 (t, 1H), 8.9 (s, 1H),8.62 (s, 1H), 8.4 (d, 1H), 7.9 (d, 1H), 7.55 (t, 1H), 7.4-7.2 (m, 5H),4.5 (d, 2H), 3.3-3.2 (m, 4H), 2.9-2.7 (m, 2H), 1.95-1.75 (m, 3H),1.5-1.35 (m, 2H). MS (EI) for C₂₅H₂₈N₆O₂: 445 (MH⁺).

3-[5-Amino-6-(morpholin-4-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.18 (t, 1H), 8.78 (s, 1H), 8.42 (s, 1H),8.1 (d, 1H), 7.88 (d, 1H), 7.55 (m, 1H), 7.38-7.24 (m, 5H), 4.55 (d,2H), 3.78-3.4 (m, 8H). MS (EI) for C₂₃H₂₃N₅O₃: 418 (MH⁺).

3-(5-Aminopyrazin-2-yl)-N-(phenylmethyl)benzamide: ¹H NMR (400 MHz,d₆-DMSO): δ 9.15 (t, 1H), 8.6 (s, 1H), 8.45 (s, 1H), 8.1 (d, 1H), 8.0(s, 1H), 7.85 (d, 1H), 7.55 (t, 1H), 7.4-7.3 (m, 5H), 6.65 (s, 2H). MS(EI) for C₁₈H₁₆N₄O: 305 (MH⁺).

1,1-Dimethylethyl3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.18 (t, 1H), 8.95 (s, 1H), 8.75 (m, 1H),8.55 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.4-7.3 (m, 4H),7.25 (m, 1H), 4.55 (m, 3H), 3.6 (m, 1H), 3.45 (m, 1H), 3.3 (m, 2H),2.15-2.0 (m, 2H), 1.4 (s, 9H). MS (EI) for C₂₈H₃₂N₆O₄: 417 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.55 (m, 2H), 9.3 (s, 1H), 8.95 (s, 1H),8.75 (s, 1H), 8.35 (d, 1H), 7.95 (d, 1H), 7.55 (t, 1H), 7.4-7.3 (m, 4H),7.25 (t, 1H), 4.7 (m, 1H), 4.5 (d, 2H), 3.4-3.2 (m, 2H) 2.3-2.1 (m, 2H),1.1 (t, 2H). MS (EI) for C₂₃H₂₄N₆O₂: 417 (MH⁺).

3-{5-Amino-6-[(4-methylpiperazin-1-yl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.75 (s, 1H), 8.45 (s, 1H),8.18 (d, 1H), 7.85 (d, 1H), 7.55 (t, 1H), 7.35-7.2 (m, 5H), 6.72 (s,2H), 4,5 (d, 2H), 3.7 (t, 2H), 3.5 (t, 2H), 2.45 (t, 2H), 2.35 (t, 2H),2.2 (s, 3H). MS (EI) for C₂₄H₂₆N₆O₂: 431 (MH⁺).

3-(5-Amino-6-{[4-(4-fluorophenyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.75 (s, 1H), 8.45 (t, 1H),8.18 (tt, 1H), 7.85 (tt, 1H), 5.75 (t, 1H), 7.3 7.2 (m, 5H), 7.0 (m,4H), 6.8 (s, 2H), 4.5 (d, 2H), 3.82 (t, 2H), 3.65 (t, 2H), 3.25 (t, 2H),3.15 (t, 2H). MS (EI) for C₂₉H₂₇N₆O₂F: 511 (MH⁺).

3-(5-Amino-6-{[4-(phenylmethyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide: ¹H NMR (400 MHz, d₆-DMSO): δ9.15 (t, 1H), 8.7 (s, 1H), 8.4 (t, 1H), 8.05 (d, 1H), 7.85 (d, 1H), 7.55(t, 1H), 7.35-7.2 (m, 10H), 6.7 (s, 2H), 4.5 (d, 2H), 3.7 (t, 2H), 3.5(m, 4H), 2.5-2.4 (m, 4H). MS (EI) for C₃₀H₃₀N₆O₂: 507 (MH⁺).

MethylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glycinate:¹H NMR (400 MHz, d₆-DMSO): δ 9.22 (t, 1H), 9.15 (t, 1H), 8.92 (s, 1H),8.5 (s, 1H), 8.36 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 4.5 (d, 2H),4.05 (d, 2H), 3.65 (s, 3H). MS (EI) for C₂₂H₂₁N₅O₄: 420 (MH⁺).

N-{[3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glycine:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.93 (s, 1H), 8.7 (s, 1H),8.35 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 4.55 (d,2H), 4.0 (d, 2H). MS (EI) for C₂₁H₁₉N₅O₄: 406 (MH⁺).

Methyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-L-prolinate:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (m, 1H), 8.85-8.75 (s, 1H), 8.45-8.35(s, 1H), 8.12-7.95 (d, 1H), 7.88 (d, 1H), 7.6 (m, 1H), 7.4-7.25 (m, 5H),5.25 (m, 1H), 4.5 (m, 4H), 4.0 (t, 1H), 3.6 (s, 3H), 2.4-2.25 (m, 1H),2.0-1.75 (m, 4H). MS (EI) for C₂₅H₂₅N₅O₄: 460 (MH⁺).

3-[(6aS)-6,11-dioxo-5,6a,7,8,9,11-hexahydro-6H-pyrazino[2,3-e]pyrrolo[1,2-a][1,4]diazepin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 11.3 (s, 1H), 9,3 (s, 1H), 9.2 (t, 1H), 8.7(s, 1H), 8.3 (d, 1H), 8.0 (d, 1H), 7.7 (t, 1H), 6.4-6.2 (m, 5H), 4.5 (m,3H), 3.7 (m, 1H), 3.5 (m, 1H), 3.0 (s, 1H), 2.0-1.8 (m, 3H). MS (EI) forC₂₄H₂₁N₅O₃: 428 (MH⁺).

Methyl1-{[3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidine-3-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.75 (d, 1H), 8.42 (d, 1H),8.08 (t, 1H), 7.85 (d, 1H), 7.55 (m, 1H), 7.35-7.25 (m, 5H), 6.72 (d,2H), 4.5 (d, 2H), 4.1-3.9 (m, 1H), 3.65 (m, 2H), 3.45 (s, 2H), 3.25-3.05(m, 2H), 2.75 (m, 1H), 2.0 (m, 1H), 1.8-1.5 (m, 3H). MS (EI) forC₂₆H₂₇N₅O₄: 474 (MH⁺).

1,1-Dimethylethyl4-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-pyrazin-2-yl]carbonyl}piperazine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.72 (s, 1H), 8.6 (s, 1H),8.05 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 6.75 (s,2H), 4.5 (d, 2H), 3.65 (t, 2H), 3.5-3.35 (m, 6H), 1.4 (s, 9H). MS(EI)for C₂₈H₃₂N₆O₄: 417 (MH⁺).

3-[5-Amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.75 (br s, 2H), 9.1 (t, 1H), 8.8 (s, 1H),8.45 (s, 1H), 8.05 (d, 1H), 7.86 (d, 1H), 7.55 (t, 1H), 7.35-7.2 (m,5H), 4.5 (d, 2H), 3.95 (t, 2H), 3.8 (t, 2H), 3.25 (t, 2H), 3.15 (t, 2H).MS (EI) for C₂₃H₂₄N₆O₂: 417 (MH⁺).

3-(5-Amino-6-cyanopyrazin-2-yl)-N-(phenylmethyl)benzamide: ¹H NMR (400MHz, d₆-DMSO): δ 9.21-9.16 (m, 1H), 8.99 (s, 1H), 8.46-8.43 (m, 1H),8.13-8.09 (m, 1H), 7.94-7.90 (m, 1H), 7.61-7.52 (m, 3H), 7.37-7.31 (m,4H), 7.28-7.22 (m, 1H), 4.55-4.49 (m, 2H). MS (EI) for C₁₉H₁₅N₅O: 330(MH⁺).

N-{[3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-L-glutamicacid: ¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.95 (s, 1H), 8.9 (d,1H), 8.55 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2(m, 5H), 4.5 (d, 2H), 4.45 (t, 1H), 2.35 (m, 2H), 2.3-2.05 (m, 2H). MS(EI) for C₂₄H₂₃N₅O₆: 478 (MH⁺).

EthylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-L-tyrosinate:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.98 (s, 1H), 8.68 (d, 1H),8.58 (s, 1H), 8.22 (d, 1H), 7.92 (d, 1H), 7.65 (t, 1H), 7.4-7.2 (m, 5H),7.12 (d, 2H), 6.65 (d, 2H), 4.6 (m, 4H), 4.15 (m, 4H), 3.1 (d, 2H), 1.2(t, 3H). MS (EI) for C₃₀H₂₉N₅O₅: 540 (MH⁺).

N-{[3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}tyrosine:¹H NMR (400 MHz, d₆-DMSO): δ 9.22 (t, 1H), 8.94 (s, 1H), 8.64 (d, 1H),8.56 (s, 1H), 8.18 (d, 1H), 7.92 (d, 1H), 7.62 (t, 1H), 7.38-7.22 (m,5H), 7.1 (d, 2H), 6.64 (d, 2H), 4.62-4.44 (m, 3H), 3.12 (d, 2H). MS (EI)for C₂₈H₂₅N₅O₅: 512 (MH⁺).

1,1-Dimethylethyl[3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)propyl]carbamate:¹H NMR (400 MHz, d₆-DMSO): δ 9.16 (t, 1H), 9.0 (t, 1H), 8.93 (s, 1H),8.54 (s, 1H), 8.44 (d, 1H), 7.9 (d, 1H), 7.58 (t, 1H), 7.38-7.23 (m,5H), 6.9 (t, 1H), 4.55 (d, 2H), 3.35 (m, 2H), 3.0 (q, 2H), 1.65 (q, 2H),1.38 (s, 9H). MS (EI) for C₂₇H₃₂N₆O₄: 405 (MH⁺).

3-Amino-N-(3-aminopropyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.55 (t, 1H), 9.3 (t, 1H), 8.92 (s, 1H),8.7 (s, 1H), 8.35 (m, 1H), 8.0 (s, 2H), 7.9 (m, 1H), 7.55 (t, 1H),7.4-7.2 (m, 5H), 4.5 (d, 2H), 3.45 (m, 2H), 2.85 (m, 2H), 1.85 (m, 2H).MS (EI) for C₂₂H₂₄N₆O₂: 405 (MH⁺).

1-{[3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidine-3-carboxylicacid: ¹H NMR (400 MHz, d6-DMSO): δ 9.15 (t, 1H), 8.7 (s, 1H), 8.45 (s,1H), 8.05 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 6.7 (s,2H), 4.5 (d, 2H), 4.45-4.2 (m, 1H), 3.9-3.6 (m, 1H), 3.3 (m, 1H), 3.1(m, 1H), 2.6 (m, 1H), 2.0 (m, 1H), 1.8-1.5 (m, 3H). MS(EI) forC₂₅H₂₅N₅O₄: 460 (MH⁺).

1,1-Dimethylethyl[2-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)ethyl]carbamate:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.95 (s, 1H), 8.95 (t, 1H),8.55 (s, 1H), 8.42 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H),7.02 (t, 1H), 4.5 (d, 2H), 3.4 (m, 2H), 3.2 (m, 2H), 1.4 (s, 9H). MS(EI)for C₂₆H₃₀N₆O₄: 391 (MH⁺).

3-Amino-N-(2-aminoethyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.6 (t, 1H), 9.3 (t, 1H), 8.95 (s, 1H),8.75 (s, 1H), 8.37 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H),4.5 (d, 2H), 3.62 (t, 2H), 3.04 (t, 2H). MS(EI) for C₂₁H₂₂N₆O₂: 391(MH⁺).

1,1-Dimethylethyl(1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidin-4-yl)carbamate:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.75 (s, 1H), 8.4 (s, 1H),8.07 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 6.95 (d,1H), 6.7 (s, 2H), 4.5 (d, 2H), 4.4 (m, 1H), 3.8 (mi, 1H), 3.6 (m, 1H),3.2 (m, 1H), 3.05 (m, 1H), 1.9-1.7 (m, 2H), 1.5-1.3 (m, 2H), 1.4 (s,9H). MS(EI) for C₂₉H₃₄N₆O₄: 431 (MH⁺).

3-{5-Amino-6-[(4-aminopiperidin-1-yl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.23 (t, 1H), 8.75 (s, 1H), 8.42 (s, 1H),8.25 (t, 3H), 8.05 (d, 1H), 7.95 (d, 1H), 7.57 (t, 1H), 7.4-7.2 (m, 5H),4.5 (d, 2H), 3.9 (m, 1H), 3.7-3.5 (m, 1H), 3.35 (m, 1H), 3.2 (m, 1H),2.95 (m, 1H), 2.1-1.9 (m, 2H), 1.7-1.5 (t, 2H). MS(EI) for C₂₄H₂₆N₆O₂:431 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.1 (d, 1H), 8.95 (s, 1H), 8.75 (d, 1H),8.55 (s, 1H), 8.35 (d, 1H), 7.93 (d, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 4H),5.6 (q, 1H), 4.4 (m, 1H), 3.1-3.0 (m, 3H1), 2.9-2.8 (m, 3H), 2.15-2.0(m, 2H), 1.8 (m, 2H). MS (EI) for C₂₅H₂₆N₆O₂: 443 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.96 (s, 1H), 8.9 (d, 1H), 8.85 (q, 1H),8.6 (s, 1H), 8.35 (d, 1H), 7.95-7.85 (q, 2H), 7.6 (m, 1H), 7.3-7.15 (m,4H), 6.65 (m, 1H), 5.6 (q, 1H), 4.65-4.5 (m, 1H), 4.15-3.95 (m, 1H), 3.8(m, 2H), 3.6 (m, 1H), 3.05-2.8 (m, 2H), 2.3-2.0 (m, 4H). MS (EI) forC₃₀H₂₈N₆O₄: 537 (MH⁺).

N-[3-(Acetylamino)propyl]-3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 9.0 (t, 1H), 8.95 (s, 1H),8.6 (s, 1H), 8.4 (d, 1H), 7.95 (t, 1H), 7.9 (d, 1H), 7.6 (t, 1H),7.4-7.25 (m, 5H), 4.55 (d, 2H), 3.35 (q, 2H), 3.15 (q, 2H), 1.8 (s, 3H),1.65 (m, 2H). MS (EI) for C₂₄H₂₆N₆O₃: 447 (MH⁺).

3-Amino-N-{3-[(furan-2-ylcarbonyl)amino]propyl}-6-(3-{[phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.16 (t, 1H), 9.05 (t, 1H), 8.95 (s, 1H),8.6 (s, 1H), 8.5 (t, 1H), 8.44 (d, 1H), 7.92 (d, 1H), 7.84 (s, 1H), 7.6(t, 1H), 7.35-7.24 (m, 5H), 7.1 (d, 1H), 6.62 (m, 1H), 4.54 (d, 2H),3.42-3.28 (m, 4H), 1.78 (m, 2H). MS (EI) for C₂₇H₂₆N₆O₄: 499 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.95-8.9 (m, 2H), 8.85-8.75 (dd, 1H), 8.7(m, 211), 8.55 (d, 1H), 8.45 (s, 1H), 7.95 (t, 1H), 7.6 (t, 1H), 7.5 (d,1H), 7.45 (d, 1H), 7.25 (m, 411), 5.6 (q, 1H), 4.55-4.5 (m, 1H), 3.9-3.4(m, 3H), 3.1-2.9 (m, 3H), 2.25-1.95 (m, 3H), 1.35 (m, 21H). MS (EI) forC₃₁H₂₉N₇O₃: 548 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-4-ylcarbonyl)amino]propyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 9.05 (t, 1H), 8.95 (s, 1H),8.88 (t, 1H), 8.7 (d, 2H), 8.58 (s, 1H), 8.45 (d, 1H), 7.92 (d, 1H),7.75 (d, 2H), 7.6 (t, 1H1), 7.35-7.25 (m, 5H), 4.55 (d, 2H), 3.4 (m,4H), 1.85 (m, 2H). MS (EI) for C₂₈H₂₇N₇O₃: 510 (MH⁺).

N-[3-({[3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)propyl]quinoxaline-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.45 (s, 1H), 9.2 (t, 1H), 9.1 (t, 1H),9.05 (t, 1H), 8.9 (s, 1H), 8.5 (s, 1H), 8.4 (d, 1H), 8.15 (m, 2H), 7.95(m, 2H), 7.85 (d, 1H), 7.55 (t, 1H), 7.35-7.15 (m, 5H), 4.5 (d, 2H),3.5-3.4 (m, 4H), 1.85 (m, 2H). MS (EI) for C₃₁H₂₈N₈O₃: 561 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[3-({[6-(trifluoromethyl)pyridin-3-yl]carbonyl}amino)propyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 2H), 9.0 (m, 2H), 8.9 (s, 1H),8.55 (s, 1H), 8.4 (m, 2H), 7.95 (d, 1H), 7.35 (d, 1H), 7.55 (t, 1H),7.35-7.15 (m, 5H), 4.5 (d, 2H), 3.4 (m, 4H), 1.8 (m 2H). MS (EI) forC₂₉H₂₆N₇O₃F₃: 578 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(quinolin-8-ylsulfonyl)amino]propyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 9.05 (m, 1H), 8.9 (s, 1H),8.8 (t, 1H), 8.5 (m, 2H), 8.35 (q, 2H), 8.25 (d, 1H), 7.9 (d, 1H), 7.7(m, 2H), 7.55 (t, 1H), 7.35-7.2 (m, 5H), 4.55 (d, 2H), 3.25 (q, 2H),2.85 (q, 2H), 1.6 (q, 2H). MS (EI) for C₃₁H₂₉N₇O₄S: 596 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-2-ylsulfonyl)amino]propyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.3 (t, 1H), 8.95 (m, 2H), 8.7 (d, 1H), 8.6(s, 1H), 8.35 (d, 1H), 8.05 (t, 1H), 7.9 (m, 3H), 7.65-7.55 (m, 2H),7.4-7.25 (m, 5H), 4.55 (d, 2H), 3.3 (q, 2H), 3.0 (q, 2H), 1.7 (q, 2H).MS (EI) for C₂₇H₂₇N₇O₄S: 546 (MH⁺).

3-Amino-N-[3-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)propyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 9.05 (t, 1H), 8.95 (s, 1H),8.55 (s, 1H), 8.4 (d, 1H), 7.9 (d, 1H), 7.6 (s, 1H), 7.5 (t, 1H),7.35-7.2 (m, 5H), 6.35 (t, 1H), 4.55 (d, 2H1), 3.35 (m, 2H), 3.15 (q,2H), 2.25 (s, 3H), 2.05 (s, 3H), 1.65 (q, 2H). MS (EI) for C₂₈H₃₀N₈O₄:543 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-4-ylcarbonyl)amino]ethyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 9.05 (t, 1H), 9.0 (t, 1H),8.95 (s, 1H), 8.7 (d, 2H), 8.6 (s, 1H), 8.4 (d, 1H), 7.9 (d, 1H), 7.75(d, 2H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 4.5 (d, 2H), 3.5 (t, 4H).MS(EI) for C₂₇H₂₉N₇O₃: 496 (MH⁺).

3-Amino-N-{2-[(furan-2-ylcarbonyl)amino]ethyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 9.05 (t, 1H), 8.95 (s, 1H),8.65 (t, 1H), 8.6 (s, 1H), 8.4 (d, 1H), 7.9 (d, 1H), 7.82 (d, 1H), 7.57(t, 1H), 7.35-7.2 (m, 5H), 7.06 (d, 1H), 6.6 (d, 1H), 4.5 (d, 2H), 3.5(t, 4H). MS(EI) for C₂₆H₂₄N₆O₄: 485 (MH⁺).

N,N′-Cyclohexane-1,2-diylbis[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide]:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 2H), 8.9 (s, 2H), 8.75 (d, 2H),8.57 (s, 2H), 8.4 (d, 2H), 7.9 (d, 2H), 7.57 (t, 2H), 7.35-7.2 (m, 10H),4.55 (d, 4H), 4.0 (m, 2H), 2.05 (d, 2H), 1.8 (d, 2H), 1.6 (m, 2H), 1.4(t, 2H). MS(EI) for C₄₄H₄₂N₁₀O₄: 775 (MH⁺).

N-[2-(Acetylamino)ethyl]-3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.25 (t, 1H), 8.98 (t, 1H), 8.95 (s, 1H),8.6 (s, 1H), 8.4 (d, 1H), 8.16 (t, 1H), 7.9 (d, 1H), 7.57 (t, 1H),7.35-7.2 (m, 5H), 4.55 (d, 2H), 3.4 (t, 2H), 3.27 (t, 2H), 1.8 (s, 3H).MS(EI) for C₂₃H₂₄N₆O₃: 433 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(quinolin-8-ylsulfonyl)amino]ethyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.9 (s, 1H), 8.8 (d, 1H), 8.7(t, 1H), 8.5 (s, 1H), 8.3 (m, 3H), 8.2 (d, 1H), 7.9 (d, 1H), 7.65 (t,1H), 7.57 (t, 1H), 7.4-7.2 (m, 7H), 4.55 (d, 2H), 3.35 (t, 2H), 3.05 (t,2H). MS(EI) for C₃₀H₂₇N₇O₄S: 582 (MH⁺).

N-[2-({[3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)ethyl]quinoxaline-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.45 (s, 1H), 9.35 (t, 1H), 9.15 (t, 1H),9.07 (t, 1H), 8.95 (s, 1H), 8.57 (s, 1H), 8.4 (d, 1H), 8.2 (t, 2H), 8.0(t, 2H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 4.5 (d, 2H), 3.6(t, 4H). MS(EI) for C₃₀H₂₆N₈O₃: 547 (MH⁺).

3-Amino-N-(2-{[(2-chloropyridin-3-yl)carbonyl]amino}ethyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 9.0 (t, 1H), 8.95 (s, 1H), 8.8(t, 1H), 8.6 (s, 1H), 8.45 (dd, 1H), 8.4 (d, 1H), 7.9 (m, 2H), 7.57 (t,1H), 7.45 (m, 1H), 7.35-7.2 (m, 5H), 4.5 (d, 2H), 3.5 (t, 411). MS(EI)for C₂₇H₂₄N₇O₃Cl: 530 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-2-ylsulfonyl)amino]ethyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 8.9 (s, 1H), 8.85 (t, 1H),8.63 (d, 1H), 8.5 (s, 1I1), 8.37 (d, 1H), 8.1 (t, 1H), 8.0 (m, 2H), 7.9(m, 2H), 7.57 (m, 2H), 7.35-7.2 (m, 5H), 4.55 (d, 2H), 3.4 (t, 2H), 3.2(t, 2H). MS(EI) for C₂₆H₂₅N₇O₄S: 532 (MH⁺).

3-Amino-N-[2-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)ethyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 9.05 (t, 1H), 8.95 (s, 1H,8.6 (s, 1H), 8.4 (d, 1H1), 7.9 (d, 1H), 7.6 (s, 1H), 7.5 (t, 1H),7.35-7.2 (m, 5H), 6.55 (t, 1H), 4.5 (d, 2H), 3.4 (t, 2H), 3.3 (t, 2H),2.15 (s, 3H), 1.96 (s, 3H). MS(EI) for C₂₇H₂₈N₈O₄: 529 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.21-9.16 (m, 1H), 8.92 (s, 1H), 8.58-8.55(m, 1H), 8.38-8.32 (m, 2H), 8.15-7.50 (bs, 2H), 7.79 (s, 1H), 7.60-7.54(m, 1H), 7.38-7.31 (m, 4H), 7.28-7.22 (m, 1H), 4.58-4.53 (m, 2H). MS(EI) for C₁₉H₁₇N₅O₂: 348 (MH⁺).

3-Amino-N-[3-({[4-(dimethylamino)phenyl]carbonyl}amino)propyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (q, 2H), 8.95 (s, 1H), 8.6 (s, 1H),8.45 (d, 1H), 8.25 (t, 1H), 7.9 (d, 1H), 7.7 (d, 2H), 7.6 (t, 1H),7.35-7.2 (m, 5H), 6.65 (d, 2H), 4.45 (d, 2H), 3.35 (m, 4H), 2.95 (s,6H), 1.75 (m, 2H). MS (EI) for C₃₁H₃₃N₇O₃: 552 (MH⁺).

1,1-Dimethylethyl4-[(3S)-3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.95 (s, 1H), 8.65 (d, 1H),8.55 (s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.7 (s, 1H), 7.55 (t, 1H),7.35-7.2 (m, 5H), 4.55 (d, 2H), 4.5 (m, 1H), 3.8 (d, 2H), 2.9-2.7 (m,3H), 2.55 (m, 1H), 2.25-2.1 (m, 2H), 1.9-1.75 (m, 3H), 1.4 (s, 9H), 1.25(m, 2H). MS (EI) for C₃₃H₄₁N₇O₄: 600 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-piperidin-4-ylpyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.65-9.45 (t, 1H), 9.3 (m, 2H), 8.98 (d,1H), 8.75 (m, 2H), 8.5-8.3 (dd, 1H), 7.9 (t, 1H), 7.55 (m, 1H), 7.4-7.25(m, 4H), 4.95-4.7 (m, 1H), 4.55 (m, 2H), 3.4 (m, 6H), 3.1 (m, 1H), 2.9(m, 2H), 2.35-1.9 (m, 6H). MS (EI) for C₂₈H₃₃N₇O₂: 500 (MH⁺).

1,1-Dimethylethyl(2R)-2-{[(3S)-3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]methyl}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.93 (s, 1H), 8.6 (d, 1H),8.55 (s, 1H), 8.25 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H),4.55 (d, 2H), 4.4 (m, 1H), 3.8 (m, 1H), 3.2 (t, 2H), 2.8 (t, 2H),2.6-2.4 (m, 4H), 2.2 (m, 1H), 1.9-1.7 (m, 5H), 1.4 (s, 9H). MS(EI) forC₃₃H₄₁N₇O₄: 600 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{(3S)-1-[(2R)-pyrrolidin-2-ylmethyl]pyrrolidin-3-yl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 11.4 (m, 1H), 9.7-9.4 (m, 3H), 9.35 (d,1H), 8.96 (s, 1H), 8.8-8.7 (m, 1H), 8.5-8.3 (m, 1H), 7.9 (d, 1H); 7.57(t, 1H), 7.35-7.2 (m, 5H), 5.0-4.7 (m, 1H), 4.5 (d, 2H), 4.0-3.6 (m,3H), 3.2 (m, 3H), 2.6 (m, 1H), 2.4-2.1 (m, 3H), 2.0-1.6 (m, 3H). MS(EI)for C₂₈H₃₃N₇O₂: 500 (MH⁺).

3-Amino-N-((3S)-1-{[4-(dimethylamino)phenyl]methyl}pyrrolidin-3-yl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.9 (s, 1H), 8.6 (d, 1H), 8.57(s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.35-7.2 (m, 5H), 7.1(d, 2H), 6.63 (d, 2H), 4.55 (d, 2H), 4.4 (m, 1H), 3.45 (m, 2H), 2.82 (s,6H), 2.7 (t, 2H), 2.4 (m, 1H), 2.2 (m, 1H), 1.82 (m, 1H). MS(EI) forC₃₂H₃₅N₇O₂: 550 (MH⁺).

3-Amino-N-{2-[({[4-(dimethylamino)phenyl]amino}carbonyl)amino]ethyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15 (t, 1H), 9.05 (t, 1H), 8.95 (s, 1H),8.6 (s, 1H), 8.42 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.45 (m, 2H),7.35-7.2 (m, 5H), 6.57 (t, 1H), 4.5 (d, 2H), 3.4 (m, 4H), 3.05 (s, 6H).MS(EI) for C₃₀H₃₂N₈O₃: 553 (MH⁺).

3-Amino-N-[2-({[4-(dimethylamino)phenyl]carbonyl}amino)ethyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.3 (t, 1H), 9.15 (t, 1H), 8.95 (s, 1H),8.68 (s, 1H), 8.45 (m, 2H), 7.9 (d, 1H), 7.7 (d, 2H), 7.57 (t, 1H),7.35-7.2 (m, 5H), 6.65 (d, 2H), 4.45 (d, 2H), 3.5 (t, 4H), 2.95 (s, 6).MS(EI) for C₃₀H₃₁N₇O₃: 538 (MH⁺).

3-Amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.93 (s, 1H), 8.65 (d, 1H),8.56 (s, 1H), 8.48 (m, 1H), 8.32 (d, 1H), 7.9 (d, 1H), 7.72 (m, 2H), 7.6(t, 1H), 7.46 (d, 1H), 7.38-7.32 (m, 4H), 7.28-7.22 (m, 2H), 4.55 (d,2H), 4.44 (m, 1H), 3.75 (s, 2H), 2.86-2.64 (m, 2H), 2.64-2.52 (m, 2H),2.2 (m, 1H). MS (ESI-LCMS) for C₂₉H₂₉N₇O₂: 508 (MH⁺).

MethylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}threoninate:¹H NMR (400 MHz, d₆-DMSO): δ 9.17 (m, 1H), 9.00 (s, 1H), 8.64 (m, 1H),8.52 (s, 1H), 8.19 (m, 1H), 7.93 (m, 1H), 7.74-7.62 (m, 3H), 7.37-7.25(m, 5H), 5.41 (m, 1H), 4.55-4.50 (m, 3H), 4.32-4.29 (m, 1H), 3.70 (m,3H), 1.16 (m, 2H). MS (EI) for C₂₄H₂₅N₅O₅: 464 (MH⁺).

3-(Ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 12.0-10.0 (s, 1H), 9.25-9.15 (tt, 1H1),9.05 (m, 1H), 9.0 (s, 1H), 8.65-8.55 (m, 1H), 8.3 (t, 1H), 7.9 (d, 1H),7.55 (q, 1H), 7.35-7.2 (m, 5H), 4.75-4.5 (m, 1H1), 4.5 (d, 2H), 3.9-3.05(m, 9 H), 2.3-2.1 (m, 1H), 1.2 (q, 6H). MS (EI) for C₂₇H₃₂N₆O₂: 473(MH⁺).

3-Amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.9 (s, 1H), 8.6 (d, 1H), 8.53(s, 1H), 8.3 (d, 1H), 7.88 (d, 1H), 7.56 (t, 1H), 7.38-7.2 (m, 5H), 4.55(d, 2H), 4.35 (m, 1H), 2.65 (m, 2H), 2.55-2.35 (m, 4H), 2.15 (m, 1H),1.8 (m, 1H), 1.0 (t, 3H). MS (EI) for C₂₅H₂₈N₆O₂: 445 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (m, 2H), 8.6 (d, 1H), 8.55 (s, 1H),8.3 (d, 1H), 7.9 (d, 1H), 7.55 (t, 1H), 7.3-7.15 (m, 4H), 5.6 (q, 1H),4.4 (m, 1H), 3.0 (m, 1H), 2.85 (m, 1H1), 2.7 (m, 1H), 2.6 (m, 1H),2.5-2.45 (m, 5H), 2.15 (m, 1H), 2.05 (m, 1H), 1.8 (m, 1H), 1.05 (t, 3H).MS (EI) for C₂₇H₃₀N₆O₂: 471 (MH⁺).

6-(3-{[(1S)-2,3-Dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-3-(ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (s, 2H), 8.75 (t, 1H), 8.7 (d, 1H), 8.6(s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 1H), 5.6(q, 1H), 4.4 (m, 1H), 3.5 (m, 4H), 3.05 (m, 1H), 2.9 (m, 2H), 2.8-2.4(m, 5H), 2.2-2.0 (m, 2H), 1.8 (m, 1H), 1.2 (t, 3H), 1.05 (t, 3H). MS(EI) for C₂₉H34N₆O₂: 499 (MH⁺).

3-Amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.5-9.2 (m, 2H), 9.0 (m, 2H), 8.7 (s, 1H),8.55 (d, 1H), 8.4 (d, 1H), 7.95 (d, 1H), 7.55 (t, 1H), 7.3-7.15 (m, 4H),5.5 (m, 1H), 4.6 (m, 1H), 4.55 (m, 1H), 3.3-3.05 (m, 5H), 2.95-2.9 (m,1H), 2.2 5(m, 1H) and 2.1 (m, 1H). MS (EI) for C₂₅H₂₆N₆O₃: 459 (MH⁺).

1,1-Dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.97 (s, 1H), 8.95 (d, 1H), 8.7 (d, 1H),8.6 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.3-7.1 (m, 4H),5.6 (t, 1H), 4.45 (t, 1H), 3.6-3.2 (m, 4H), 3.05-2.8 (m, 2H), 2.5 (m,1H), 2.2-1.9 (m, 3H), 1.4 (s, 9H). MS(EI) for C₃₀H₃₄N₆O₄: 443 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.98 (s, 1H), 8.95 (d, 1H), 8.78 (t, 1H),8.57 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.42-7.2 (m,5H), 5.2 (t, 1H), 4.5 (t, 1H), 3.65-3.25 (m, 4H), 2.2-2.0 (m, 2H), 1.5(d, 3H), 1.4 (s, 9H). MS(EI) for C₂₉H₃₄N₆O₄: 431 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate: ¹H NMR (400 MHz, d₆-DMSO): δ8.9 (t, 1H), 8.75 (t, 1H), 8.3-8.1 (m, 2H), 7.57 (t, 1H), 7.45 (m, 1H),7.3-7.1 (m, 4H), 4.82 (t, 1H), 4.65-4.4 (m, 2H), 3.6-3.2 (m, 6H), 2.9(m, 2H), 2.2-2.0 (m, 2H), 1.4 (s, 9H). MS(EI) for C₃₀H₃₄N₆O₄: 443 (MH⁺).

1,1-Dimethylethyl(3S)-3-({[3-amino-6-(3-([(2-phenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (s, 1H), 8.7 (m, 2H), 8.45 (s, 1H),8.35 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.35-7.2 (m, 5H), 4.5 (t, 1H),3.6-3.45 (m, 4H), 3.4-3.25 (m, 2H), 2.9 (t, 2H), 2.2-2.0 (m, 2H), 1.4(s, 9H). MS(EI) for C₂₉H₃₄N₆O₄: 431 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.98 (s, 1H), 8.95 (d, 1H), 8.75 (t, 1H),8.57 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.45-7.2 (m,5H), 5.22 (t, 1H), 4.5 (t, 1H), 3.65-3.45 (m, 2H), 3.3 (m, 2H), 2.2-2.0(m, 2H), 1.55 (s, 3H), 1.4 (s, 9H). MS(EI) for C₂₉H₃₄N₆O₄: 431 (MH⁺).

3-Amino-6-[3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.6 (t, 1H), 9.35 (t, 1H), 9.0-8.9 (m, 2H),8.4 (d, 1H), 8.2 (s, 1H), 7.57 (t, 1H), 7.42 (d, 1H), 7.35-7.0 (m, 4H),4.8 (s, 1H), 4.6 (m, 2H), 3.9-3.6 (m, 2H), 3.4-3.1 (m, 4H), 2.9 (t, 2H),2.25 (t, 1H), 2.05 (t, 1H). MS(EI) for C₂₅H₂₆N₆O₂: 443 (MH⁺).

3-Amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.65 (t, 1H), 9.4 (t, 1H), 9.2 (d, 1H), 9.1(t, 1H), 8.95 (s, 1H), 8.75 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.57(t, 1H), 7.35-7.2 (m, 5H), 4.7 (t, 1H), 3.6-3.2 (m, 6H), 2.9 (t, 2H),2.3 (t, 1H), 2.1 (t, 1H). MS(EI) for C₂₄H₂₆N₆O₂: 431 (MH⁺).

3-Amino-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.75 (t, 1H), 9.55 (t, 1H), 9.3 (m, 2H),8.99 (s, 1H), 8.8 (s, 1H), 8.4 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.45(m, 3H), 7.38-7.2 (m, 3H), 5.25 (t, 1H), 4.7 (t, 1H), 3.6-3.2 (m, 411),2.3 (t, 1H), 2.15 (t, 1H), 1.6 (s, 3H). MS(EI) for C₂₄H₂₆N₆O₂: 431(MH⁺).

3-Amino-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.7 (t, 1H), 9.45 (t, 1H), 9.25 (m, 2H),9.0 (s, 1H), 8.78 (s, 1H), 8.4 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.5(m, 2H), 7.35-7.2 (m, 3H), 5.25 (t, 1H), 4.7 (t, 1H), 3.6-3.2 (m, 4H),2.3 (t, 1H), 2.1 (t, 1H), 1.6 (s, 3H). MS(EI) for C₂₄H₂₆N₆O₂: 431 (MH⁺).

3-(5-Amino-6-cyanopyrazin-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.99 (s, 1H), 8.96-8.89 (m, 1H), 8.48-8.43(m, 1H), 8.13-8.07 (m, 1H), 7.98-7.92 (m, 1H), 7.63-7.48 (m, 3H),7.32-7.16 (m, 4H), 5.66-5.56 (m, 1H), 3.07-2.96 (m, 1H), 2.94-2.80 (m,1H), 2.54-2.43 (m, 1H), 2.08-1.95 (m, 1H). MS (EI) for C₂₁H₁₇N₅O: 356(MH⁺).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (s, 1H), 8.65-8.6 (m, 3H), 8.32 (d,1H), 7.95 (d, 1H), 7.6 (t, 1H), 7.3-7.2 (m, 4H), 5.5 (m, 1H), 4.55 (m,1H1), 4.35 (m, 1H), 3.1 (dd, 1H), 3.0-2.85 (m, 4H), 2.75 (m, 3H), 2.0(m, 1H), and 1.7 (m, 1H). MS (EI) for C₂₅H₂₆N₆O₃: 459 (MH⁺).

3-Amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1S,2R)-2-hydroxy-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (s, 1H), 8.7-8.6 (m, 3H), 8.35 (d, 1H),7.95 (d, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 4H), 5.5 (m, 1H), 5.15 (s, 1H),4.55 (s, 1H), 4.4 (m, 1H), 3.1 (dd, 1H), 2.95 (ss, 1H), 2.75 (m, 1H),2.6 (s, 1H), 2.5 (m, 4H), 2.2 (m, 1H), 1.9 (m, 1H), 1.05 (t, 3H). MS(EI) for C₂₇H₃₀N₆O₃: 487 (MH⁺).

1,1-Dimethylethyl3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (m, 2H), 8.55 (m, 2H), 8.3 (d, 1H),7.95 (d, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 4H), 5.6 (q, 1H), 3.9-3.6 (m,3H), 3.3 5(s, 3H), 3.1-2.85 (m, 4H), 2.0 (m, 1H), 1.85 (m, 1H), 1.7 (m,2H), 1.3 (s, 9H). MS (EI) for C₃₁H₃₆N₆O₄: 457 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.5-9.2 (m, 2H), 9.05 (m, 1H), 8.95 (s,1H), 8.85 (t, 1H:), 8.55 (d, 1H), 8.35 (d, 1H), 7.95 (d, 1H), 7.6 (t,1H), 7.25 (m, 4H), 5.6 (m, 1H), 5.0 (s, 1H), 4.3 (s 1H), 3.3-3.0 (m,4H), 2.9 (m, 1H), 2.7 (m, 1H), 2.5 (m, 1H), 2.1 (m, 1H), 1.95-1.65 (m,4H). MS (EI) for C₂₆H₂₈N₆O₂: 457 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-(1-ethylpiperidin-3-yl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (m, 2H), 8.55 (m, 2H), 8.25 (d, 1H),7.92 (d, 1H), 7.6 (t, 1H), 7.25 (m, 4H), 5.6 (q, 1H), 4.0 (m, 1H), 3.05(m, 1H), 2.9 (m, 1H), 2.7 (m, 1H), 2.35 (m, 2H), 2.2 (s, 2H), 2.05 (m,1H), 1.7-1.5 (m, 4H), 1.25 (s, 1H), 1.0 (t, 3H). MS (EI) for C₂₈H₃₂N₆O₂:485 (MH⁺).

3-Amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1R,2S)-2-hydroxy-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MH, d₆-DMSO): δ 8.97 (s, 1H), 8.65 (m, 3H), 8.3 (d, 1H),7.96 (d, 1H), 7.7 (s, 1H), 7.6 (t, 1H), 7.25 (m, 4H), 5.5 (m, 1H), 5.2(d, 1H), 4.55 (s, 1H), 4.4 (m, 1H), 3.1 (dd, 1H), 2.95 (s, 1H), 2.7 (m,2H), 2.55-2.4 (m, 4H), 2.15 (m, 1H), 1.85 (m, 1H), 1.05 (t, 3H). MS (EI)for C₂₇H₃₀N₆O₃: 487 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-pyrimidin-4-ylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.9 (s, 1H), 9.2 (s, 2H), 9.04 (d, 1H),8.9 (d, 1H), 8.65 (s, 1H), 8.4 (d, 2H), 8.05 (d, 1H), 7.7 (t, 1H), 7.3(m, 4H), 5.7 (m, 1H), 3.15-2.9 (m, 2H), 2.1 (m, 1H). MS (EI) forC₂₅HI₂₁N₇O₂: 452 (MH⁺).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide:¹H NMR 7.9 (d, 1H), 7.5 (t, 1H), 7.4 (s, 1H), 7.15 (m, 4H), 5.45 (m,1H), 4.45 (t, 1H), 3.1 (m, 1H), 2.9 (m, 3H). MS (EI) for C₂₆H₂₅N₇O₃: 484(MH⁺).

1,1-Dimethylethyl(3S)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrrolidine-1-carboxylate;¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (m, 1H), 8.9 (d, 2H), 8.53 (s, 1H),8.35 (d, 1H), 7.9 (d, 1H), 7.55 (t, 1H), 7.3-7.15 (m, 4H), 5.6 (q, 1H),3.35 (d, 2H), 3.2 (m, 2H), 3.0 (m, 3H), 2.85 (m, 2H), 2.5 (m, 1H), 2.0(m, 1H), 1.9 (m, 1H), 1.65 (m, 1H), 1.4 (s, 9H). MS (EI) for C₃₁H₃₆N₆O₄:457 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.4 (t, 2H), 9.22 (t, 1H), 9.05 (d, 1H),8.95 (s, 1M), 8.6 (s, 1H), 8.5 (d, 1H), 7.95 (d, 1H), 7.6 (t, 1H), 7.45(s, 2H), 7.3-7.15 (m, 4H), 5.6 (q, 1H), 3.4 (t, 2H), 3.25 (m, 2H),3.15-2.8 (m, 4H), 2.6 (m, 1H), 2.45 (m, 2H), 2.1 (m, 1H), 2.0 (m, 1H),1.7 (m, 1H). MS (EI) for C₂₆H₂₈N₆O₂: 457 (MH⁺).

3-Amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]phenyl}-N-piperidin-3-ylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.96 (s, 1H), 8.89 (d, J=8.4 Hz, 1H), 8.72(d, J=8.0 Hz, 1H), 8.54 (s, 1H), 8.35 (d, J=7.2 Hz, 1H), 7.93 (d, J=8.0Hz, 1H), 7.60 (t, J=9.6 Hz, 1H), 7.30 (m, 1H), 7.25 (m, 1H), 5.61 (q,J=8 Hz, 1H), 4.20 (m, 1H), 3.29 (m, 1H), 3.01 (m, 2H), 2.89 (m, 1H),2.03 (m, 1H), 1.90 (m, 1H), 1.74 (m, 2H). MS(E) for C₂₆H₂₈N₆O₂: 457(MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.96 (s, 1H), 8.89 (d, J=8.2 Hz, 1H), 8.71(m, 1H), 8.55 (s, 1H), 8.35 (d, J=7.6 Hz, 1H), 7.93 (d, J=8.0 Hz, 1H),7.60 (t, J=8.0 Hz, 1H), 7.25 (m, 2H), 5.60 (q, J=8.4 Hz, 1H), 4.2 (m,1H), 3.29 (m, 1H), 3.01 (m, 2H), 2.89 (m, 1H), 2.03 (m, 1H), 1.90 (m,1H) 1.72 (m, 1H). MS(EI) for C₂₆H₂₈N₆O₂: 457 (MH⁺).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-piperidin-3-ylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (s, 1H), 8.75 (d, 1H), 8.65 (s, 1H),8.5 (m, 1H), 8.35 (d, 1H), 8.0 (d, 1H), 7.6 (t, 1H), 7.25 (m, 4H), 5.5(m, 1H), 4.55 (m, 1H), 4.25 (m, 1H), 3.5-2.7 (m, 7H), 1.9 (m, 2H), 1.7(m, 2H). MS (EI) for C₂₆H₂₈N₆O₃: 473 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.05 (t, 2H), 8.9 (d, 2H), 8.55 (s, 1H),8.35 (d, 1H), 7.95 (d, 11), 7.6 (t, 1H), 7.5 (s, 1H), 7.3-7.2 (m, 4H)5.62 (q, 1H), 3.6 (q, 2H), 3.05-2.85 (m, 5H), 2.0 (m, 1H). MS (EI) forC₂₆H₂₅N₇O₂: 468 (MH⁺).

3-Amino-N-azepan-4-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.4 (s, 1H), 9.25 (s, 1H), 9.0 (m, 1H), 8.9(s, 1H), 8.7 (d, 1H), 8.6 (s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.55 (t,1H), 7.3-7.1 (m, 4H), 5.6 (q, 1H), 4.1 (s, 1H), 3.25 (m, 1H), 3.1-2.8(m, 3H), 2.45 (m, 1H), 2.0-1.7 (m, 8H). MS (EI) for C₂₇H₃₀N₆O₂: 471(MH⁺).

1,1-Dimethylethyl(3S)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.05 (m, 1H), 9.0 (s, 1H), 8.65 (s, 1H),8.6 (d, 1H), 8.4 (d, 1H), 7.98 (d, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 4H),5.5 (m, 1H), 5.65 (d, 1H), 4.55 (m, 1H), 3.4 (m, 2H), 3.35 (m, 3H),3.35-3.0 (m, 3H), 2.9 (d, 1H), 1.9 (m, 1H), 1.6 (m, 1H), 1.4 (m, 9H). MS(EI) for C₃₁H₃₆N₆O₅: 473 (MH⁺).

1,1-Dimethylethyl4-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)azepane-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (m, 2H), 8.65-8.55 (dd, 2H), 8.35 (d,1H), 7.95 (d, 1H), 7.7 (s, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 4H), 5.6 (q,1H), 3.95 (m, 1H), 3.6-3.5 (m, 1H), 3.4-3.1 (m, 3H), 3.05 (m, 1H), 2.9(m, 1H), 2.05-1.4 (m, 7H), 1.4 (s, 9H). MS (EI) for C₃₂H₃₈N₆O₄: 471(MH⁺).

1,1-Dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.91 (s, 1H), 8.87 (d, J=8.0 Hz, 1H), 8.51(m, 1H), 8.27 (d, J=6.4 Hz, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.56 (t, J=8.0Hz, 1H), 7.27 (m, 1H), 7.21 (m, 1H), 5.60 (q, J=8.8 Hz, 1H), 2.97 (m,2H), 2.03 (m, 2H), 1.84 (m, 2H), 1.69 (m, 2H), 1.33 (s, 9H). MS (EI) forC₃₁H₃₆N₆O₄: 501 (M-C₄H₉).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.98 (s, 1H), 8.62 (s, 1H), 8.58 (m, 2H),8.28 (d, J=6.40 Hz, 1H), 7.93 (d, J=8.0 Hz, 1H), 7.56 (t, 8.0 Hz, 1H),7.22 (m, 4H), 5.48 (m, 1H), 4.54 (m, 1H), 3.85 (m, 2H), 3.71 (m, 2H),3.10 (m, 2H), 2.91 (m, 2H), 1.86 (m, 1H), 1.71 (m, 2H), 1.36 (s, 9H). MS(EI) for C₃₁H₃₆N₆O₅: 517 (MH⁺-C₄H₉).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.1 (t, 1H), 8.95 (s, 1H), 8.65 (d, 2H),8.5 (d, 1H), 7.95 (d, 1H), 7.55 (t, 1H), 7.25-7.15 (m, 4H), 5.5 (m, 1H),5.0 (s, 1H1), 4.55 (m, 1H), 3.3 (m, 2H), 3.15-2.8 (m, 4H), 2.85 (m, 1H),1.9 (m, 1H), 1.8 (s, 4H), 1.6 (m, 1H). MS (EI) for C₂₆H₂₈N₆O₃: 473(MH⁺).

1,1-Dimethylethyl4-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]azepane-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (s, 1H), 8.7-8.65 (m, 3H), 8.45 (d,1H), 7.95 (d, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 4H), 5.5 (m, 1H), 4.55 (m,1H), 3.95 (m, 1H), 3.6-3.1(m, 5H), 2.95 (d, 1H), 2.05-1.6 (m, 6H), 1.4(s, 9H). MS (EI) for C₃₂H₃₈N₆O₅: 487 (MH⁺).

3-Amino-N-azepan-4-yl-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.98 (s, 1H), 8.95 (d, 1H), 8.7 (s, 1H),8.6 (d, 1H), 8.3 (d, 1H), 7.95 (d, 1H), 7.6 (t, 1H), 7.3-7.15 (m, 4H),5.5 (m, 1H), 4.55 (m, 1H), 4.2 (m, 1H), 3.1 (dd, 1H), 3.0-2.7 (m, 4H),1.95-1.55 (m, 9H). MS (EI) for C₂₇H₃₀N₆O₃: 487 (MH⁺).

3-Amino-N-azepan-4-yl-6-{3-[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2-d][1,3]oxazol-2-yl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.4-9.25 (dd, 1H), 8.9 (s, 1H), 8.65 (s,1H), 8.25 (d, 1H), 7.8 (m, 1H), 7.55 (t, 1H), 7.4 (m, 1H), 7.3 (m, 4H),5.75 (d, 1H), 5.6 (t, 1H), 4.3 (m, 1H), 3.55 (dd, 1H), 3.3 (s, 1H),3.2-2.9 (m, 4H), 2.7 (m, 1H), 1.9 (m, 2H), 1.65 (m, 311). MS (EI) forC₂₇H₂₈N₆O₂: 469 (MH⁺).

1,1-Dimethylethyl(3R)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (m, 1H), 8.9 (d, 2H), 8.55 (s, 1H),8.35 (d, 1H), 7.9 (d, 1H), 7.55 (t, 1H), 7.3-7.15 (m, 4H), 5.6 (q, 1H),3.35 (m, 3H), 3.2 (m, 1H), 3.0 (m, 2H), 2.9 (m, 1H), 2.5 (m, 3H), 2.0(m, 1H), 1.9 (m, 1H), 1.675 (m, 1H), 1.4 (s, 9H). MS (EI) forC₃₁H₃₆N₆O₄: 557 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.35 (s, 2H), 9.15 (t, 1H), 9.0 (d, 1H),8.85 (s, 1H), 8.6 (s, 1H), 8.4 (d, 1H), 7.9 (d, 1H), 7.55 (t, 1H),7.3-7.15 (m, 4H), 5.6 (q, 1H), 4.9 (s, 1H), 3.4 (t, 2H), 3.15-2.85 (m,4H), 2.65-2.45 (m, 4H), 2.15-1.9 (m, 2H), 1.7 (m, 1H). MS (EI) forC₂₆H₂₈N₆O₂: 457 (MH⁺).

1,1-Dimethylethyl(3R)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (m, 1H), 8.95 (s, 1H), 8.65 (s, 1H),8.57 (d, 1H), 8.4 (d, 1H), 7.95 (d, 1H), 7.55 (t, 1H), 7.3-7.15 (m, 4H),5.5 (m, 1H), 5.1 (d, 1H), 4.55 (m, 1H), 3.35 (m, 5H), 3.25-3.05 (m, 3H),2.9 (d, 1H), 2.5 (m, 1H), 1.9 (m, 1H), 1.65 (m, 1H), 1.4 (s, 9H). MS(EI) for C₃₁H₃₆N₆O₅: 473 (MH⁺).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.1 (m, 3H), 9.0 (s, 1H), 8.65 (d, 2H), 8.4(d, 1H), 7.95 (d, 1H), 7.55 (t, 1H), 7.3-7.15 (m, 4H), 5.5 (m, 1H), 5.4(s, 1H), 4.55 (t, 1H), 3.55 (s, 1H), 3.4 (m, 2H), 3.3-3.05 (m, 4H), 2.95(d, 2H), 2.6 (m, 1H), 2.0 (m, 1H), 1.7 (m, 1H). MS (EI) for C₂₆H₂₈N₆O₃:473 (MH⁺).

1,1-Dimethylethyl(3R)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate:¹H NMR (400 MH, d₆-DMSO): δ 8.91 (s, 1H), 8.87 (d, J=8.0 Hz, 1H), 8.51(m, 1H), 8.27 (d, J=6.4 Hz, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.56 (t, J=8.0Hz, 1H), 7.27 (m, 1H), 7.21 (m, 1H), 5.60 (q, J=8.8 Hz, 1H), 2.97 (m,2H), 2.03 (m, 2H), 1.84 (m, 2H), 1.69 (m, 2H), 1.33 (s, 9H). MS (EI) forC₃₁H₃₆N₆O₄: 501 (M-C₄H₉).

1,1-Dimethylethyl(3R)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.91 (s, 2H), 8.72 (d, J=8.8 Hz, 1H), 8.51(m, 1H), 8.28 (d, J=7.6 Hz, 1H), 7.90 (d, J=7.6 Hz, 1H), 7.56 (t, J=8.0Hz, 1H), 7.27 (m, 2H), 7.19 (m, 2H), 5.60 (m, 4H), 3.81 (m, 2H), 3.71(m, 2H), 3.00 (m, 2H), 2.91 (m, 2H), 2.01 (m, 1H), 1.86 (m, 1H), 1.71(m, 2H), 1.36 (s, 9H). MS (EI) for C₃₁H₃₆N₆O₅: 473 (MH⁺-C₅H₉O₂).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.02 (m, 1H), 8.91 (s, 1H), 8.87 (s, 1H),8.85 (m, 1H), 8.73 (d, J=8.4 Hz, 1H), 8.65 (s, 1H), 8.57 (m, 1H), 8.52(m, 1H), 8.43 (m, 1H), 8.35 (d, J=8.0 Hz, 1H), 7.95 (m, 1H), 7.91 (m,1H), 7.62 (m, 2H), 7.36 (t, 8.4 Hz, 1H), 7.17 (m, 1H), 4.62 (d, J=6.0Hz, 1H), 3.07 (m, 2H), 2.38 (s, 3H), 1.92 (m, 2H), 1.75 (m, 2H). MS (EI)C₂₃H₂₆N₈O₂: 447 (MH⁺).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.01(s, 1H), 8.76 (d, J=8.4 Hz, 1H), 8.67(m, 1H), 8.62 (d, J=8.8 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.60 (t, 7.6Hz, 2H), 7.28 (m, 2H), 7.22 (m, 2H), 5.51 (m, 1H), 5.18 (m, 1H), 4.56(m, 1H), 4.23 (m, 1H), 3.15 (m, 2H), 2.96 (m, 2H), 2.72 (m, 1H), 1.88(m, 2H), 1.71 (m, 2H), 1.23 (s, 1H). MS (EI) for C₂₆H₂₈N₆O₃: 473 (MH⁺).

3-(5-Amino-6-{(1E)-N-[4-(1-methylethyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, CDCl₃): δ 8.40 (m, 1H), 8.0 (m, 2H), 7.80 (m, 2H), 7.25(m,1H), 7.2 (m, 4H), 6.9 (m, 4H), 4.8 (s, 2H), 2.6 (s, 3H), 2.0 (s, 1H)1.2 (m, 6H). MS (EI) for C₂₉H₃₀N₆O: 479 (MH⁺).

3-{5-Amino-6-[(1E)-N-1,3-benzothiazol-2-ylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.40 (m, 1H), 8.0 (m, 2H), 7.80 (m, 2H),7.25 (m, 1H), 7.2 (m, 4H), 6.9 (m, 4H), 4.5 (s, 2H), 2.8 (s, 3H). MS(EI) for C₂₇H₂₃N₇OS: 494 (MH⁺).

3-{5-Amino-6-[(1E)-N-(4-methylphenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.90 (d, 1H), 9.80 (d, 1H), 9.20 (d, 1H),8.50 (d, 2H), 8.20 (d, 1H), 7.90 (m, 1H), 7.75-7.0 (m, 7H), 4.50 (d,2H), 2.6 (s, 3H), 1.30 (s, 3H). MS (EI) for C₂₇H₂₆N₆O: 451 (MH⁺).

3-{5-Amino-6-[(1E)-N-(4-chlorophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.80 (s, 1H), 9.10 (m, 1H), 8.65 (s, 1H),8.55 (s, 1H), 8.2 (d, 1H), 7.90 (d, 1H), 7.60 (m, 1H), 7.4-7.1 (m, 8H),4.50 (d, 2H), 3.2 (s, 3H), 2.6 (s, 3H). MS (EI) for C₂₇H₂₃ClN₆O: 472(MH⁺).

3-{5-Amino-6-[(1E)-N-methyl-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide: ¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (m, 1H),9.00 (d, 1H), 8.80 (d, 1H), 8.20 (dd, 2H), 7.95 (d, 2H), 7.60 (d, 1H),7.45-7.0 (m, 6H), 4.50 (d, 2H), 3.2 (s, 3H), 2.6 (s, 3H). MS (EI) forC₂₇H₂₆N₆O: 451(MH⁺).

3-{5-Amino-6-[(1E)-N-(2-hydroxyethyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (m, 1H), 8.45 (m, 2H), 8.15 (d, 1H),7.80 (d, 1H), 7.45-7.15 (m, 5H), 4.50 (d, 2H), 3.6 (m, 2H), 3.3 (m, 2H),2.2 (s, 3H). MS (EI) for C₂₂H₂₄N₆O₂: 405 (MH⁺).

3-{5-Amino-6-[(1E)-N-morpholin-4-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (m, 1H), 8.8 (s, 1H), 8.65 (m, 1H),8.2 (m,1H), 7.8 (m, 1H), 7.4 (m, 1H), 7.2 (m, 4H), 4.8 (s, 2H), 3.8 (m,4H), 3.2 (m, 2H), 2.8 (m, 2H), 2.6 (s, 3H). MS (EI) for C₂₄H₂₆N₆O₂: 431(MH⁺).

4-((2E)-2-{1-[3-Amino-6-(3-[[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]ethylidene}hydrazino)benzoicacid: ¹H NMR (400 MHz, d₆-DMSO): δ 10.0 (s, 1H), 9.2 (m, 1H), 8.8 (s,1H), 8.5 (s, 1H1), 8.2 (m, 1H), 7.8 (m, 3H), 7.60 (m, 1H), 7.25 (m, 3H),7.2 (m, 3H), 4.6 (s, 2H), 2.8 (s, 3H). MS (EI) for C₂₇H₂₄N₆O₃: 481(MH⁺).

Ethyl((2E)-2-{1-[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]ethylidene}hydrazino)acetate:¹H NMR (400 MHz, d₄-MeOH): δ 8.40 (m, 1H), 8.2 (m, 2H), 7.9 (m, 1H),7.80 (m, 1H), 7.35 (m, 1H), 7.2 (m, 4H), 4.6 (s, 2H), 4.2 (m, 2H), 3.8(s, 2H), 2.4 (s, 3H), 1.2 (m, 3H). MS (EI) for C₂4H₂₆N₆O₃: 447 (MH⁺).

3-{5-Amino-6-[(1E)-N,N-dimethylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide: ¹H NMR (400 MHz, CDCl₃): δ 9.2 (s, 1H), 9.0(s, 1H), 8.40 (m, 1H), 8.2 (m, 1H), 7.80 (m, 2H), 7.25 (m, 1H), 7.2 (m,3H), 4.8 (s, 2H), 3.3 (s, 6H), 2.6 (s, 3H). MS (EI) for C₂₂H₂₄N₆O: 389(MH⁺).

3-(5-Amino-6-{(1E)-N-[hydrazino(imino)methyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 9.2 (s, 1H), 8.8 (s, 1H), 8.6 (m, 1H), 8.2(m, 2H), 7.80 (m, 1H), 7.25 (m, 1H), 7.2 (m, 3H), 4.6 (s, 2H), 2.8 (s,3H). MS (EI) for C₂₁H₂₃N₉O: 418 (MH⁺).

3-(5-Amino-6-{(1E)-N-[4-(methylsulfonyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.0 (s, 1H), 9.2 (m, 1H), 8.8 (s, 1H), 8.5(s, 1H), 8.2 (m, 1H), 7.8 (m, 2H), 7.6 (m, 1H), 7.25 (m, 3H), 7.2 (m,3H), 4.6 (s, 2H), 3.2 (s, 3H), 2.8 (s, 3H). MS (EI) for C₂₇H₂₆N₆O₃S: 515(MH⁺).

3-{5-Amino-6-[(1E)-N-(4-cyanophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.1 (s, 1H), 9.20 (m, 1H), 8.70 (s, 1H),8.55 (s, 1H), 8.20 (d, 1H), 7.95 (d, 1H), 7.75 (d, 2H), 7.60 (m, 1H),7.40-7.20 (m, 8H), 4.50 (d, 2H), 2.6 (s, 3H). MS (EI) for C₂₇H₂₃N₇O: 462(MH⁺).

3-{5-Amino-6-[(1E)-N-pyridin-2-ylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide: ¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (m, 1H),8.75 (s, 1H), 8.55 (s, 1H), 8.20 (d, 2H), 7.95-7.85 (m, 3H), 7.60 (m,1H), 7.40-7.20 (m, 5H), 4.50 (d, 2H), 2.6 (s, 3H). MS (EI) forC₂₅H₂₃N₇O: 438 (MH⁺).

3-(5-Amino-6-{(1E)-N-[amino(imino)methyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d6-DMSO): δ 11.0 (m, 1H), 9.20 (m, 1H), 8.80 (s, 1H),8.75 (s, 1H), 8.20 (d, 2H), 8.00-7.85 (m, 5H), 7.60 (m, 1H), 7.40-7.20(m, 4H), 4.50 (d, 2H), 2.6 (s, 3H). MS (EI) for C₂₁H₂₂N₈O: 403 (MH⁺).

3-[5-Amino-6-((1E)-N-{4-[(trifluoromethyl)oxy]phenyl}ethanehydrazonoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.1 (s, 1H), 9.90 (s, 1H), 9.20 (m, 1H),8.70 (s, 1H), 8.55 (s, 1H), 8.20 (d, 1H), 7.95 (d, 2H), 7.60 (m, 2H),7.40-7.20 (m, 6H), 4.50 (d, 2H), 2.6 (s, 3H). MS (EI) for C₂₇H23F₃N₆O₂:522 (MH⁺).

3-{5-Amino-6-[(1E)-N-(4-nitrophenyl)ethanehydrazanoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.5 (s, 1H), 9.20 (m, 1H), 8.70 (s, 1H),8.55 (s, 1H), 8.20 (m, 3H), 7.95 (d, 2H), 7.60 (m, 1H), 7.40-7.20 (m,7H), 4.50 (d, 2H), 2.6 (s, 3H). MS (EI) for C₂₆H₂₅N₇O₃: 483 (MH⁺).

3-(5-Amino-6-{(1E)-N-[4-(trifluoromethyl)pyrimidin-2-yl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d6-DMSO): δ 8.95 (m, 1H), 8.55 (s, 1H), 8.40 (s, 1H),8.20 (d, 1H), 7.95 (d, 1H), 7.60 (m, 1H), 7.40-7.20 (m, 5H), 4.50 (s,2H), 2.6 (s, 3H). MS (EI) for C₂₅H₂₁F₃N₈O: 507 (MH⁺).

3-(5-Amino-6-{(1E)-N-[(dimethylamino)carbonothioyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.90 (s, 1H), 9.20 (m, 1H), 8.70 (s, 1H),8.55 (s, 1H), 8.20 (d, 1H), 7.95 (d, 1H), 7.60 (m, 1H), 7.40-7.20 (m,6H), 4.50 (d, 2H), 3.4 (s, 6H), 2.6 (s, 3H). MS (EI) for C₂₃H₂₅N₇OS: 448(MH⁺).

3-{5-Amino-6-[(1E)-N-1H-1,2,3-benzotriazol-1-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d6-DMSO): δ 9.20 (m, 1H), 9.00 (s, 1H), 8.60 (s, 1H),8.20 (d, 1H), 8.10 (s, 2H), 7.90 (dd, 2H), 7.70-7.60 (m, 2H), 7.50 (m,1H), 7.40-7.20 (m, 6H), 4.50 (d, 2H), 2.95 (s, 3H). MS (EI) forC₂₆H₂₂N₈O: 463 (MH⁺).

3-{5-Amino-6-[(1E)-N-methylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.50 (d, 1H), 8.30 (s, 1H), 8.20 (d, 1H),7.90 (d, 1H), 7.65 (m, 1H), 7.40-7.20 (m, 5H:), 4.50 (d, 2H), 2.40 (s,3H), 1.95 (s, 3H). MS (EI) for C₂₁H₂₂N₆O: 375 (MH⁺).

3-(5-Amino-6-{(1E)-N-[4-(trifluoromethyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.0 (s, 1H), 9.2 (m, 1H), 8.8 (s, 1H), 8.5(s, 1H), 8.2 (m, 1H), 7.8 (m, 2H), 7.6 (m, 1H), 7.25 (m, 3H), 7.2 (m,3H), 4.6 (s, 2H), 2.8 (s, 3H). MS (EI) for C₂₇H₂₃N₆OF₃: 505 (MH⁺).

3-{5-Amino-6-[(1E)-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.0 (s, 1H), 9.2 (m, 1H), 8.8 (s, 1H), 8.5(s, 1H), 8.2 (m, 1H), 7.8 (m, 2H), 7.6 (m, 1H), 7.25 (m, 4H), 7.2 (m,3H), 4.6 (s, 2H), 2.8 (s, 3H). MS (EI) for C₂₆H₂₄N₆O: 437 (MH⁺).

3-{5-Amino-6-[(1E)-N-(4-methylpiperazin-1-yl)ethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (m, 1H), 8.8 (s, 1H), 8.65 (m, 1H),8.2 (m, 1H), 7.8 (m, 1H), 7.4 (m, 1H), 7.2 (m, 4H), 4.8 (s, 2H), 3.6 (m,2H), 3.4 (m, 2H), 3.2 (m, 2H), 3.0 (m, 2H), 2.8 (s, 3H), 2.6 (s, 3H). MS(EI) for C₂₅H₂₉N₇O: 444 (MH⁺).

3-[5-Amino-6-((1E)-N-{(2R)-2-[(methyloxy)methyl]pyrrolidin-1-yl}ethanimidoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.65 (m, 1H), 8.3 (m,1H), 8.2 (m,1H), 7.8(m, 1H), 7.6 (m, 1H), 7.4 (m, 4H), 7.2 (m, 1H), 4.8 (s, 2H), 3.6 (m,2H), 3.4 (s, 3H), 3.2 (m, 2H), 3.1 (m, 1H), 2.6 (s, 3H), 2.0 (m, 4H). MS(EI) for C₂₆H₃₀N₆O₂: 459 (MH⁺).

3-{5-Amino-6-[(1E)-N-azepan-1-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.65 (m, 1H), 8.3 (m, 1H), 8.2 (m, 1H), 7.8(m, 1H), 7.6 (m, 1H), 7.4 (m, 4H), 7.2 (m, 1H), 4.8 (s, 2H), 3.8 (m,4H), 2.6 (s, 3H) 2.2 (m, 4H), 1.8 (m, 4H). MS (EI) for C₂6H₃₀N₆O: 443(MH⁺).

3-(5-Amino-6-{(E)-[(phenylmethyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (m, 1H), 8.55 (s, 1H), 8.40 (d, 1H),8.30 (m, 1H), 8.10 (d, 1H), 7.80 (m, 2H ), 7.60-7.20 (m, 13H), 4.50-4.40(dd, 4H). MS (EI) for C₂₆H₂₄N₆O: 437 (MH⁺).

3-[5-Amino-6-((E)-{[amino(imino)methyl]hydrazono}methyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 11.7 (s, 1H), 9.20 (m,1H), 8.80 (s, 1H),8.50 (m, 1H), 8.40 (m, 2H), 8.15 (d, 1H), 7.95 (m, 3H), 7.60 (m, 1H),7.40-7.20 (m, 6H), 4.50 (d, 2H). MS (ED for C₂₀H₂₀N₈O: 389 (MH⁺).

3-(5-Amino-6-{(E)-[(2-hydroxyethyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MH, d₆-DMSO): δ 9.20 (m, 1H), 8.50 (m, 2H), 8.20 (d, 1H),7.90 (m, 2H), 7.40-7.20 (m, 5H), 4.50 (d, 2H), 3.60 (m, 2H), 3.30 (m,2H). MS (EI) for C₂₁H₂₂N₆O₂: 391 (MH⁺).

3-{5-Amino-6-[(E)-(pyridin-2-ylhydrazono)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide: ¹H NMR (400 MHz, d₆-DMSO): δ 11.3 (s, 1H),9.20 (m, 1H), 8.85 (s, 1H), 8.50 (s, 1H), 8.35 (s, 1H), 8.20 (dd, 2H),7.75-7.50 (m, 3H), 7.40-7.20 (m, 5H), 7.10 (d, 1H), 6.95 (m, 1H), 4.50(d, 2H). MS (EI) for C₂₄H₂₁N₇O: 424 (MH⁺).

3-(5-Amino-6-{(E)-[(4-cyanophenyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 11.5 (s, 1H), 9.20 (m,1H), 8.70 (s, 1H),8.50 (s, 1H), 8.35 (s, 1H), 8.20 (d, 1H), 7.95 (d, 1H), 7.80-7.55 (m,5H), 7.40-7.00 (m, 7H), 4.50 (d, 2H). MS (EI) for C₂₆H₂₁N₇O: 448 (MH⁺).

3-(5-Amino-6-1{(E)-[(4-methylphenyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.8 (s,1H), 9.20 (m,1H), 8.60 (s, 1H),8.50 (s, 1H), 8.20 (m, 2H), 7.95 (d, 1H), 7.50 (m, 2H), 7.40-6.90 (m,6H), 4.50 (d, 2H), 2.10 (s, 3H). MS (EI) for C₂₆H₄₂N₆O: 437 (MH⁺).

3-{5-Amino-6-[(E)-(hydroxyimino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 11.9 (s, 1H), 9.20 (s, 1H), 8.75 (s, 1H),8.55 (s, 1H), 8.30 (s, 1H), 8.10 (d, 1H), 7.90 (s, 1H), 7.65-7.15 (m,7H), 4.50 (d, 2H). MS (EI) for C₁₉H₁₇N₅O₂: 348 (MH⁺).

Ethyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]methyl}piperidine-4-carboxylate:¹H NMR (400 MHz, d₄-MeOH): δ 8.63 (s, 1H), 8.48 (s, 1H), 8.14 (m, 1H),7.84 (m, 1H), 7.57 (t, 1H), 7.31-7.38 (m, 4H), 7.23-7.27 (m, 1H), 4.61(s, 2H), 4.43 (s, 2H), 4.16-4.23 (m, 2H), 3.88-3.91 (m, 1H), 3.41-3.68(m, 1H), 3.29-3.31 (m, 5H), 2.65-2.83 (m, 1H), 2.01-2.32 (m, 4H). MS(EI) for C₂₇H₃₁N₅0₃: 474 (MH⁺).

3-[5-Amino-6-(hydroxymethyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide: ¹HNMR (400 MHz, d₄-MeOH): δ 8.40-8.47 (m, 1H), 8.34 (s, 1H1), 8.11-8.14(m, 1H), 7.86-7.88 (m, 1H), 7.56 (m, 1H), 7.31-7.38 (m, 4H) 7.25-7.26(m, 1H1), 4.82 (s, 2H), 4.61 (s, 2H). MS (EI) for C₁₉H₁₈N₄O₂: 432(MH⁺).

3-{5-Amino-6-[(4-pyridin-2-ylpiperazin-1-yl)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.62 (s, 1H), 8.56 (s, 1H), 8.07-8.16 (m,3H), 7.58-7.87 (m, 1H), 7.56 (t, 1H), 7.35-7.41 (m, 3H), 7.26-7.30 (m,2H), 7.16-7.19 (m, 2H), 4.61 (s, 2H), 4.53 (s, 2H), 4.05 (s, 4H),3.71-3.73 (m, 4H). MS (EI) for C₂₈H₂₉N₇O: 480(MH⁺).

3-(5-Amino-6-{[3-(hydroxymethyl)piperidin-1-yl]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.63 (s, 1H), 8.51 (t, 1H), 8.13-8.15 (m,1H), 7.85-7.87 (m, 1H), 7.55-7.59 (m, 1H), 7.32-7.39 (m, 4H), 7.20-7.28(m, 1H), 4.59-4.70 (m, 2H), 4.41 (s, 2H), 4.05-4.08 (m, 1H), 3.75-3.78(m, 1H), 3.51-3.58 (m, 1H), 3.34-3.40 (m, 1H), 3.12-3.17 (m, 1H), 2.89(t, 1H), 1.77-2.16 (m, 4H), 1.30-1.36 (m, 1H). MS (ESI-LCMS) forC₂₅H₂₉N₅O₂: 432 (MH⁺).

1,1-Dimethylethyl(3S)-3-{[(3-amino-6-(3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.06 (t, 1H), 8.95 (s, 1H), 8.7 (d, 1H),8.5 (s, 1H), 8.3 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.25 (d, 2H), 6.85(d, 2H), 4.5 (d, 2H), 3.7 (s, 3H), 3.6-3.2 (m, 4H), 2.2-2.0 (m, 2H), 1.4(s, 9H). MS (EI) for C₂₉H₃₄N₆O₅: 447 (MH⁺).

1,1-Dimethylethyl(3S)-3-({[3-amino-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.23 (t, 1H), 8.95 (s, 1H), 8.75 (d, 1H),8.55 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.48 (d, 2H),7.37 (d, 2H), 4.57 (d, 2H), 4.5 (m, 1H), 3.6-3.2 (m, 4H), 2.2-2.0 (m,2H), 1.4 (s, 9H). MS (EI) for C₂₉H₃₁N₆O₅F₃: 501 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.9 (s, 1H), 8.8 (d, 1H), 8.7 (t, 1H), 8.45(s, 1H), 8.25 (d, 1H), 7.8 (d, 1H), 7.5 (t, 1H), 7.35-7.15 (m, 3H), 4.6(d, 2H), 4.4 (m, 1H), 3.6-3.2 (m, 4H), 2.1-1.9 (m, 2H), 1.35 (s, 9H). MS(EI) for C₂₈H₃₀N₆O₄Cl: 469 (MH⁺).

1,1-Dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenylpyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate: ¹H NMR (400 MHz,d₆-DMSO): δ 9.1 (t, 1H), 8.9 (s, 1H), 8.7 (d, 1H), 8.5 (s, 1H), 8.35 (d,1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.3 (d, 2H), 7.2 (d, 2H), 4.6-4.4 (m,3H), 3.6-3.2 (m, 4H), 2.4 (s, 3H), 2.2-2.0 (m, 2H), 1.4 (s, 9H). MS (EI)for C₂₉H₃₄N₆O₄S: 463 (MH⁺).

1,1-Dimethylethyl(3S)-3-{[(3-amino-6-{3-[(2,3-dihydro-1H-dien-2-ylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (s, 1H), 8.8-8.7 (m, 2H), 8.5 (s, 1H),8.3 (d, 1H), 7.83 (d, 1H:), 7.57 (t, 1H), 7.2 (m, 2H), 7.15 (m, 2H1),4.7 (m, 2H), 3.6-3.4 (m, 2H), 3.25 (m, 4H), 2.98 (m, 2H), 2.2-2.0 (m,2H), 1.4 (s, 9H). MS (EI) for C₃₀H₃₄N₆O₄: 443 (MH⁺).

3-Amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.6-9.4 (m, 3H), 9.2 (d, 1H), 8.95 (s, 1H),8.7 (s, 1H), 8.5 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.3 (d, 2H), 6.85(d, 2H), 4.7 (m, 1H), 4.4 (d, 2H), 3.7 (s, 3H), 3.4-3.1 (m, 4H), 2.25(t, 1H), 2.05 (t, 1H). MS (EI) for C₂₄H₂₆N₆O₃: 447 (MH⁺).

3-Amino-N-[(3S)-pyrrolidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.65 (t, 1H), 9.5 (m, 1H), 9.25 (m, 1H),9.2 (d, 1H), 8.95 (s, 1H), 8.75 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.57(t, 1H), 7.5 (d, 2H), 7.3 (d, 2H), 4.7 (t, 1H), 4.5 (d, 2H), 3.4-3.1 (m,4H), 2.25 (t, 1H), 2.05 (t, 1H). MS (EI) for C₂₄H₂₃N₆O₃F₃: 501 (MH⁺).

3-Amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.65 (m, 1H), 9.45 (m, 1H), 9.2 (m, 2H),8.96 (s, 1H), 8.72 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H),7.25 (t, 2H), 7.18 (d, 2H), 4.8-4.6 (m, 2H), 3.45-3.1 (m, 8H), 2.3 (t,1H), 2.1 (t, 1H). MS (EI) for C₂₅H₂₆N₆O₂: 443 (MH⁺).

3-Amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino)carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.5 (m, 1H), 9.35 (m, 1H), 9.1 (m, 2H),8.95 (s, 1H), 8.6 (s, 1H), 8.4 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H),7.4-7.2 (m, 3H), 4.65 (s, 3H), 3.4-3.2 (m, 4H), 2.3 (m, 1H), 2.05 (m,1H). MS (EI) for C₂₃H₂₂N₆O₂FCl: 469 (MH⁺).

3-Amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.25 (t, 1H), 8.9 (s, 1H), 8.86 (d, 1H),8.6 (s, 1H), 8.3 (d, 1H), 7.85 (d, 1H), 7.62 (d, 1H), 7.57 (t, 1H), 7.3(d, 2H), 7.2 (d, 2H), 4.6 (t, 1H), 4.45 (d, 2H), 3.4-3.1 (m, 4H), 2.4(s, 3H), 2.2 (m, 1H), 2.0 (m, 1H). MS (EI) for C₂₄H₂₆N₆O₂S: 463 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-({[(4-chlorophenyl)methyl)amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.95 (s, 1H), 8.75 (d, 1H),8.55 (s, 1H), 8.4 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.4 (s, 4H), 4.5(d, 2H), 4.47 (m, 1H), 3.6-3.2 (m, 4H), 2.2-2.0 (m 2H), 1.4 (s, 9H). MS(EI) for C₂₈H₃₁N₆O₄Cl: 451 (MH⁺).

1,1-Dimethylethyl(3S)-3-({[3-amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.4 (t, 1H), 8.95 (s, 1H), 8.7 (d, 2H), 8.6(s, 1H), 8.4 (d, 1H), 8.2 (m, 1H), 7.9 (d, 1H), 7.75 (d, 1H), 7.65 (t,1H), 7.6 (m, 2H), 4.75 (d, 2H), 4.5 (m, 1H), 3.6-3.2 (m, 4H), 2.2-2.0(m, 2H), 1.4 (s, 9H). MS (EI) for C₂₇H₃₁N₇O₄: 462 (MH⁺).

1,1-Dimethylethyl(3S)-3-({[3-amino-6-(3-([(pyridin-3-ylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate;¹H NMR (400 MHz, d₆-DMSO): δ 9.3 (t, 1H), 8.9 (s, 1H), 8.85 (m, 1H),8.78 (d, 1H), 8.7 (d, 1H), 8.5 (s, 1H), 8.43 (d, 1H), 8.38 (d, 1H), 7.9(m, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 4.7 (d, 2H), 4.5 (m, 1H), 3.6-3.2(m, 4H), 2.2-2.0 (m, 2H), 1.4 (s, 9H). MS (EI) for C₂₇H₃₁N₇O₄: 518(MH⁺).

1,1-Dimethylethyl(3S)-3-{[(3-amino-6-(3-[(3,4-dihydro-2H-chromen-4-ylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (m, 1H), 8.9 (s, 1H), 8.55 (s, 1H),8.38 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.22 (d, 1H), 7.17 (t, 1H),6.85 (t, 1H), 6.78 (d, 1H), 5.3 (m, 1H), 4.6-4.4 (m, 1H), 4.4-4.2 (m,2H), 3.6-3.2 (m, 4H), 2.2-2.0 (m, 4H), 1.4 (s, 9H). MS (EI) forC₃₀H₃₄N₆O₅: 459 (MH⁺).

3-Amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.55 (t, 1H), 9.37 (m, 1H), 9.1 (m, 2H),8.95 (s, 1H), 8.7 (s, 1H), 8.5 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.4(s, 4H), 4.7 (m, 1H), 4.5 (d, 2H), 3.5-3.3 (m, 3H), 3.3-3.1 (m, 1H), 2.3(m, 1H), 2.1 (m, 1H). MS (EI) for C₂₃H₂₃N₆O₂Cl: 451 (MH⁺).

3-Amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.15 (t, 1H), 9.55-9.4 (m, 2H), 9.26 (d,1H), 8.95 (m, 2H), 8.82 (d, 1H), 8.5 (m, 1H), 8.35 (d, 1H), 8.0 (d, 1H),7.9 (m, 2H), 7.57 (t, 1H), 4.9 (d, 2H), 4.75 (m, 1H), 3.4 (m, 3H), 3.2(m, 1H), 2.3 (m, 1H), 2.1 (m, 1H). MS (EI) for C₂₂H₂₃N₇O₂: 418 (MH⁺).

3-Amino-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.15 (t, 1H), 9.6 (m, 2H), 9.3 (d, 1H),9.03-8.83 (m, 4H), 8.65 (d, 1H), 8.3 (d, 1H), 8.07 (t, 1H), 7.9 (d, 1H),7.57 (t, 1H), 4.78 (m, 3H), 3.42 (m, 3H), 3.2 (m, 1H), 2.3 (m, 1H), 2.1(m, 1H). MS (EI) for C₂₂H₂₃N₇O₂: 418 (MH⁺).

3-Amino-6-{3-[(3,4-dihydro-2H-chromen-4-ylamino)carbonyl]phenyl}-N-[(3)S-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.0 (m, 2H), 8.95-8.75 (m, 3H), 8.57 (s,1H), 8.37 (d, 1H), 7.95 (d, 1H), 7.6 (t, 1H), 7.2 (m, 2H), 6.9 (t, 1H),6.82 (d, 1H), 5.35 (m, 1H), 4.6 (m, 1H), 4.3 (m, 2H), 3.4 (m, 2H), 3.25(m, 2H), 2.3-2.0 (m, 4H). MS (EI) for C₂₅H₂₆N₆O₃: 459 (MH⁺).

3-Amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (d, 1H), 8.99 (m, 2H), 8.88 (d, 1H),8.6 (s, 1H), 8.38 (d, 1H), 7.95 (d, 1H), 7.57 (t, 1H), 7.4 (d, 1H), 7.26(t, 1H), 6.95 (m, 2H), 5.85 (m, 1H), 4.8-4.5 (m, 3H), 4.4-4.0 (m, 2H),3.5-3.2 (m, 2H), 2.4-2.0 (m, 2H). MS (EI) for C₂₄H₂₄N₆O₃: 445 (MH⁺).

1,1-Dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d6-DMSO): δ 8.95 (s, 1H), 8.75 (m, 1H), 8.75 (s, 1H),8.3 (d, 1H), 7.75 (d, 1H), 7.55 (t, 1H), 7.4 (d, 2H), 7.25 (t, 2H), 7.15(m, 1H), 4.5 (m, 1H), 3.6-3.2 (m, 4H), 2.2-2.0 (m, 2H), 1.7 (s, 6H), 1.4(s, 9H). MS (EI) for C₃₀H₃₆N₆O₄: 445 (MH⁺).

3-Amino-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.1-8.9 (m, 2H), 9.0 (s, 1H), 8.95 (d, 1H),8.6 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 7.4 (d, 2H), 7.3(t, 2H), 7.2 (m, 1H), 4.6 (m, 1H), 3.5-3.2 (m, 4H), 2.3-2.1 (m, 2H), 1.7(s, 6H). MS (EI) for C₂₅H₂₈N₆O₂: 445 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.81-8.75 (m, 1H), 8.59-8.54 (m, 1H),8.26-8.18 (m, 1H), 7.90-7.85 (m, 1H), 7.61-7.54 (m, 1H), 7.34-7.16 (m,4H), 5.73-5.66 (m, 1H), 4.71-4.61 (m, 1H), 4.05-3.85 (m, 2H), 3.50-3.41(m, 1H), 3.29-2.87 (m, 6H), 2.76-2.56 (m, 2H), 2.44-2.23 (m, 1H),2.09-2.01 (m, 1H). MS (EI) for C₂₆H₂₈N₆O₂: 457 (MH⁺).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.77-8.71 (m, 1H), 8.64-8.59 (m, 1H),8.25-8.19 (m, 1H), 8.00-7.93 (m, 1H), 7.64-7.57 (m, 1H), 7.35-7.18 (m,4H), 5.64-5.59 (m, 1H), 4.79-4.60 (m, 2H), 3.96-3.84 (m, 1H), 3.49-3.40(m, 1H), 3.28-3.13 (m, 2H), 3.05-2.97 (m, 5H), 2.73-2.61 (m, 1H),2.41-2.23 (m, 1H). MS (EI) for C₂₆H₂₈N₆O₃: 473 (MH⁺).

3-Amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.8 (t, 1H), 9.5 (s, 1H), 9.3 (s, 1H), 9.2(d, 1H), 8.95 (s, 1H), 8.8 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.55 (t,1H), 7.35 (m, 2H), 4.75 (m, 1H), 4.5 (d, 2H), 3.4 (m, 3H), 3.2 (m, 1H),2.3 (m, 1H), 2.15 (m, 1H). MS (EI) for C₂₃H₂₁N₆O₂F₃: 471 (MH⁺).

3-Amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.55 (s, 1H), 9.45 (s, 1H), 9.35 (t, 1H),9.1 (d, 1H), 8.9 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.55 (t, 1H), 7.45(m, 1H), 7.12 (m, 1H), 5.0 (s, 1H), 4.65 (m, 1H), 4.55 (d, 2H),3.45-3.15 (m, 4H), 2.25 (m, 1H), 2.1 (m, 1H). MS (EI) for C₂₃H₂₁N₆O₂F₃:471 ).

3-Amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.8 (t, 1H), 9.55 (s, 1H), 9.4 (s, 1H),9.25 (d, 1H), 8.95 (s, 1H), 8.85 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H),7.55 (t, 1H), 7.45 (m, 1H), 7.15 (m, 1H), 4.75 (m, 1H), 4.55 (d, 2H),3.4 (m, 3H), 3.2 (m, 1H), 2.3 (m, 1H), 2.15 (m, 1H). MS (EI) forC₂₃H₂₁N₆O₂F₃: 471 (MH⁺).

3-Amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.7 (t, 1H), 9.5 (s, 1H), 9.3 (s, 1H), 9.2(d, 1H), 8.9 (s, 1H), 8.75 (s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.7 (d,1H), 7.55 (t, 1H), 7.4 (m, 1H), 7.3 (t, 1H), 4.7 (m, 1H), 4.5 (d, 2H),3.4 (m, 3H), 3.2 (m, 1H), 2.3 (m, 1H), 2.15 (m, 1H). MS (EI) forC₂₃H₂₂N₆O₂FBr: 515 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.16 (t, 1H), 8.9 (s, 1H), 8.7 (d, 1H),8.55 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.6 (s, 1H), 7.57 (t, 1H), 7.4(m, 2H), 4.58 (d, 2H), 4.5 (m, 1H), 3.6-3.2 (m, 4H), 2.2-2.0 (m, 2H),1.4 (s, 9H). MS (EI) for C₂₈H₃₀N₆O₄Cl₂: 485 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 9.2 (t, 1H), 8.9 (s, 1H), 8.7 (d, 1H), 8.5(s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.6 (m, 3H), 7.36 (d, 1H), 4.5 (m,3H), 3.6-3.2 (m, 4H), 2.2-2.0 (m, 2H1), 1.4 (s, 9H). MS (EI) forC₂₈H₃₀N₆O₄Cl₂: 485 (MH⁺).

3-Amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.7 (t, 1H), 9.5 (m, 1E), 9.3 (m, 1H), 9.2(d, 1H), 8.95 (s, 1H), 8.8 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.6 (s,1H), 7.57 (t, 1H), 7.4 (d, 2H), 4.7 (m, 1H), 4.55 (d, 2H), 3.5-3.1 (m,4H), 2.4-2.0 (m, 2H). MS (EI) for C₂₃H₂₂N₆O₂Cl₂: 485 (MH⁺).

3-Amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.78 (t, 1H), 9.5 (m, 1H), 9.35 (m, 1H),9.23 (d, 1H), 8.95 (s, 1H), 8.8 (s, 1H), 8.53 (d, 1H), 7.9 (d, 1H), 7.6(s, 1H), 7.6-7.5 (m, 2H), 7.4 (d, 1H), 4.7 (m, 1H), 4.5 (d, 2H), 3.5-3.1(m, 4H), 2.4-2.1 (m, 2H). MS (EI) for C₂₃H₂₂N₆O₂Cl₂: 485 (MH⁺).

3-Amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.43 (t, 1H), 9.4 (m, 1H), 9.15 (m, 1H),8.9 (s, 1H), 8.65 (s, 1H), 8.3 (d, 1H), 7.87 (d, 1H), 7.57 (t, 1H), 7.3(d, 2H), 6.85 (d, 2H), 4.45 (d, 2H), 3.7 (s, 311), 3.3-3.1 (m, 3H), 2.75(m, 1H), 1.9-1.7 (m, 4H). MS (EI) for C₂₅H₂₈N₆O₃: 461 (MH⁺).

3-Amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.65 (t, 1H), 9.3 (m, 1H), 9.05 (m, 1H),9.0-8.9 (m, 2H), 8.75 (s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.6-7.5 (m,2H), 7.4 (d, 2H), 4.6 (d, 2H), 3.3-3.1 (m, 3H), 2.75 (m, 1H), 1.9-1.7(m, 4H). MS (EI) for C₂₄H₂₄N₆O₂Cl₂: 499 (MH⁺).

3-Amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.4 (t, 1H), 9.05 (d, 1H), 8.95 (s, 1H),8.85 (d, 2H), 8.65 (s, 11), 8.35 (d, 1H1), 7.9 (d, 1H), 7.6 (t, 1H), 7.4(m, 2H), 7.15 (m, 2H), 4.5 (d, 2H), 4.25 (m, 1H), 3.25 (m, 2H), 3.1 (m,1H), 2.75 (m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₄H₂₅N₆O₂F: 449 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.55 (t, 1H), 9.15 (d, 1H), 8.95 (s, 1H),8.0 (d, 2H), 8.7 (s, 1H), 8.35 (s, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.5(d, 2H), 7.35 (d, 2H), 4.55 (d, 2H), 4.3 (m, 1H), 3.3-3.1 (m, 3H), 2.75(m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₅H₂₅N₆O₃F₃: 515 (MH⁺).

3-Amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.4 (t, 1H), 9.05 (d, 1H), 8.95 (s, 1H),9.35 (d, 2H), 8.65 (s, 1H), 8.35 (d, 1H), 7.95 (d, 1H), 7.7-7.6 (m, 5H),7.45 (m, 4H), 7.35 (m, 1H), 4.6 (d, 2H), 4.3 (m, 1H), 3.3-3.1 (m, 3H),2.75 (m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₃₀H₃₀N₆O₂: 507 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-5-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.6 (s, 1H), 9.25 (t, 1H), 8.95 (s, 1H),8.75 (d, 2H1), 8.65 (m, 1H), 8.55 (s, 1H), 8.35 (d, 1H), 8.15 (d, 1H),7.95 (d, 1H), 7.7 (s, 1H), 7.6 (t, 1H), 7.55 (d, 2H), 4.6 (d, 2H), 4.25(m, 1H), 3.3 (m, 2H), 3.05 (m, 1H), 2.75 (m, 1H), 1.95-1.65 (m, 4H). MS(EI) for C₂₆H₂₆N₈O₂S: 515 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.5 (t, 1H), 9.2 (s, 1H), 8.95 (s, 2H), 8.9(d, 1H), 8.7 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.5 (d,1H), 7.4 (m, 3H), 4.6 (d, 2H), 4.3 (m, 1H), 3.3-3.1 (m, 3H), 2.75 (m,1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₅H₂₅N₆O₂F₃: 515 (MH⁺).

3-Amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.5 (t, 1H), 9.25 (m, 1H), 9.05 (m, 1H),8.95 (s, 1H), 8.93 (d, 1H), 8.7 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.6(t, 1H), 7.5 (m, 1H), 7.25 (m, 1H), 7.1 (m, 1H), 4.55 (d, 2H), 4.3 (m,1H), 3.3-3.1 (m, 3H), 2.75 (m, 1H), 1.95-1.7 (m, 4H). MS (EI) forC₂₄H₂₄N₆O₂F₂: 467 (MH⁺).

3-Amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl)amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.5 (t, 1H), 9.15 (d, 1H), 8.95 (s, 1H),8.9 (d, 2H), 8.7 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.6 (t, 1H), 7.45(m, 2H), 7.3 (m, 1H), 4.55 (d, 2H), 4.3 (m, 1H), 3.3-3.1 (m, 3H), 2.75(m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₄H₂₄N₆O₂FCl: 483 (MH⁺).

3-Amino-6-{3-[({[4-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.55 (t, 1H), 9.05 (d, 1H), 8.95 (s, 1H),8.85 (m, 2H), 8.65 (s, 1H), 8.35 (d, 1H), 7.9 (d 1H), 7.8 (m, 2H), 7.6(t, 1H), 7.5 (t, 1H), 4.5 (d, 2H), 4.3 (m, 1H), 3.3-3.1 (m, 3H), 2.75(m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₅H₂₄N₆O₂F₄: 517 (MH⁺).

3-Amino-6-(3-{[(naphthalen-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.55 (t, 1H), 9.3 (m, 1H), 9.1 (m, 1H),9.0-8.9 (m, 2H), 8.75 (s, 1H), 8.4 (d, 1H), 8.3 (d, 1H), 8.0 (m, 2H),7.9 (d, 1H), 7.7-7.5 (m, 5H), 5.05 (d, 2H), 4.3 (m, 1H), 3.3-3.1 (m,3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS (EI) for C₂₈H₂₈N₆O₂: 481 (MH⁺).

3-Amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.05 (t, 1H), 8.9 (s, 1H), 8.8 (m, 1H), 8.7(d, 1H), 8.65 (m, 1H), 8.5 (s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.57 (t,1H), 7.25 (d, 2H), 6.85 (d, 2H), 4.4 (d, 2H), 4.25 (m, 1H), 3.4-3.0 (m,3H), 2.9 (s, 6H), 2.9-2.7 (m, 1H), 2.0-1.7 (m, 4H). MS (EI) forC₂₆H₃₁N₇O₂: 474 (MH⁺).

3-Amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.1 (t, 1H), 8.95 (s, 1H), 8.9 (m, 1H), 8.7(d, 1H), 8.5 (s, 1H), 8.35 (d, 1H), 7.85 (d, 1H), 7.57 (t, 1H), 6.9 (s,1H), 6.85 (m, 2H), 5.98 (s, 2H), 4.43 (d, 1H), 4.2 (m, 1H), 3.4-3.2 (m,2H), 3.05 (q, 1H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS (EI) for C₂₅H₂₆N₆O₄:475 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MH, d₆-DMSO): δ 9.3 (t, 1H), 9.0 (m, 1H), 8.95 (s, 1H), 8.8(m, 1H), 8.78 (d, 1H), 8.6 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.64-7.56(m, 2H), 7.51 (d, 1H), 7.6 (d, 1H), 7.4 (d, 2H), 7.1 (d, 1H), 4.55 (d,2H), 4.25 (m, 1H), 3.3-3.0 (m, 3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS(EI) for C₂₈H₂₈N₆O₂S: 513 (MH⁺).

3-Amino-6-{3-[({[2-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.26 (t, 2H), 9.03 (m, 1H), 8.95 (s, 1H),8.87 (d, 1H), 8.65 (s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.2(m, 2H), 7.0 (d, 1H), 6.9 (t, 1H), 4.5 (d, 2H), 4.3 (m, 1H), 3.8 (s,3H), 3.3-3.0 (m, 3H), 2.74 (m, 1H), 1.9-1.7 (m,4H). MS (EI) forC₂₅H₂₈N₆O₃: 461 (MH⁺).

3-Amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.3 (m, 1H), 9.1 (m, 2H), 8.95 (s, 1H), 8.9(d, 1H), 8.65 (s, 1H), 8.35 (d, 1H), 7.9 (d, 1H), 7.57 (t, 1H), 7.1 (d,1H), 6.6 (s, 1H), 6.5 (d, 1H), 4.5 (d, 2H), 4.3 (m, 1H), 3.8 (s, 6H),3.3-3.0 (m, 3H), 2.75 (m, 1H), 2.0-1.7 (m, 4H). MS (EI) for C₂₆H₃₀N₆O₄:491 (MH⁺).

3-Amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.4 (t, 1H), 9.3 (m, 1H), 9.07 (m, 1H),8.95 (s, 1H), 8.94 (d, 1H), 8.7 (s, 1H), 8.3 (d, 1H), 7.9 (d, 1H), 7.57(t, 1H), 7.3 (d, 1H), 7.25 (s, 1H), 7.2 (d, 1H), 4.45 (d, 2H), 4.3 (m,1H), 3.3-3.1 (m, 3H), 2.75 (m, 1H), 2.4 (s, 3H), 2.0-1.7 (m, 4H). MS(EI) for C₂₅H₂₇N₆O₂Cl: 479 (MH⁺).

3-Amino-6-[3-({[(2,3-difluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.5 (t, 1H), 9.3 (m, 1H), 9.05 (m, 1H),8.95 (s, 1H), 8.94 (d, 1H), 8.7 (s, 1H), 8.34 (d, 1H), 7.9 (d, 1H), 7.57(t, 1H), 7.17 (m, 1H), 7.04 (m, 1H), 4.55 (d, 2H), 4.3 (m, 1H), 3.3-3.1(m, 3H), 2.78 (m, 1H), 2.25 (s; 3H), 2.0-1.7 (m, 4H). MS (EI) forC₂₅H₂₆N₆O₂F₂: 481 (MH⁺).

3-Amino-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.79 (s, 1H), 8.55 (m, 1H), 8.23-8.20 (m,1H), 7.95-7.87 (m, 3H), 7.65-7.57 (m, 3H), 4.72 (s, 2H), 4.31-4.29 (m,1H), 3.50-3.45 (m, 2H), 3.38-3.31 (m, 2H), 3.13-2.98 (m, 5H), 2.10-1.83(m, 4H). MS (EI) for C₂₅H₂₈N₆O₄S: 510 (MH⁺).

3-Amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.78 (s, 1H), 8.53 (s, 1H), 8.19-8.17 (m,1H), 7.85-7.83 (m, 1H), 7.58-7.55 (m, 1H), 6.86-6.77 (m, 3H), 4.49 (s,2H), 4.31-4.28 (m, 1H), 4.20 (s, 4H), 3.51-3.46 (m, 1H), 3.37-3.29 (m,1H), 3.16-3.10 (m, 1H), 2.99-2.97 (m, 1H), 2.10-1.83 (m, 4H). MS (EI)for C₂₆H₂₈N₆O₄: 489(MH⁺).

3-Amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.76 (s, 1H), 8.60 (m, 1H), 8.23-8.21 (m,1H), 7.92-7.89 (m, 1H), 7.62-7.59 (m, 1H), 7.39-7.32 (m, 4H), 4.60 (s,2H), 4.31-4.29 (m, 1H), 3.50-3.46 (m, 2H), 3.37-3.30 (m, 2H), 2.10-1.83(m, 4H). MS (EI) for C₂₄H₂₅N₆O₂Cl: 465 (MH⁺).

3-Amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-ylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.79 (s, 1H), 8.61 (m, 1H), 8.23-8.20 (m,1H), 7.87-7.82 (m, 1H), 7.77-7.03 (m, 5H), 4.82 (s, 2H), 4.39-4.36 (m,1H), 3.51-3.45 (m, 2H), 3.13-2.98 (m, 2H), 2.10-1.83 (m, 4H). MS (EI)for C₂₄H₂₄N₆O₂FCl: 483 (MH⁺).

3-Amino-6-{3-[({[4-(methylthio)phenyl]methylamino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide: ¹HNMR (400 MHz, d6-DMSO): δ 9.26 (m, 1H), 8.95 (s, 1H), 8.79 (d, J=8.4 Hz,1H), 8.58 (s, 1H), 8.34 (d, J=8.0 Hz, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.94(t, J=8.0 Hz, 1H), 7.31 (m, 2H), 7.24 (m, 2H), 4.48 (d, J=6.0 Hz, 2H),4.24 (m, 1H), 3.72 (m, 1H), 3.68 (m, 1H), 3.59 (s, 2H), 3.08 (m, 2H),2.75 (m, 2H), 2.67 (m, 2H), 1.91 (m, 2H), 1.76 (m, 2H). MS (EI) forC₂₅H₂₈N₆O₂S: 477 (MH⁺).

3-Amino-6-(3-{[(1,2-diphenylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.02 (m, 1H), 8.99 (m, 1H), 8.93 (m, 1H),8.75 (m, 2H), 8.41 (m, 1H), 8.31 (m, 1H), 7.78 (m, 1H), 7.54 (m, 1H),7.50 (m, 1H), 7.35 (m, 4H), 7.25 (m, 4H), 7.15 (m, 2H), 5.32 (m, 2H),2.67 (m, 2H), 2.46 (m, 2H), 2.33 (m, 2H), 1.92 (m, 2H), 1.73 (m, 2H). MS(EI) for C₃₁H₃₂N₆O₂: 521 (MH⁺).

3-Amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.43 (m, 1H), 8.96 (s, 2H), 8.85 (m, 1H),8.64 (s, 1H), 8.35 (m, 1H), 7.92 (m, 1H), 7.61 (m, 1H), 7.10 (m, 3H),4.53 (m, 2H), 3.68 (m, 2H), 3.60 (m, 1H), 3.48 (m, 2H), 3.25 (m, 2H),1.91 (m, 2H), 1.77 (m, 2H). MS (EI) for C₂₄H₂₄F₂N₆O₂: 467 (MH⁺).

Methyl4-[({[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]carbonyl}amino)methyl]benzoate:¹H NMR (400 MHz, d₆-DMSO): δ 9.39 (m, 1H), 8.96 (s, 1H), 8.81 (d, J=8.8Hz, 1H), 8.36 (d, J =8.0 Hz, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.92 (d, J=7.6Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.52 (d, J=8.4 Hz, 2H), 4.61 (d, J=6.0Hz, 2H), 3.85 (s, 3H), 3.67 (m, 1H), 3.48 (m, 2H), 3.25 (m, 2H), 3.08(m, 2H), 2.77 (m, 2H), 1.90 (m, 2H), 1.75 (m, 2H). MS (EI) forC₂₆H₂₈N₆O₄: 489 (MH⁺).

3-Amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.47 (m, 1H), 9.11 (m, 1H), 8.95 (s, 1H),8.89 (d, J=8.8 Hz, 1H), 8.67 (s, 1H), 8.34 (d, 8.4 Hz, 1H), 7.90 (d,J=8.0 Hz, 1H), 7.59 (t, J=7.6 Hz, 1H), 7.52 (m, 2H), 7.34 (d, J=8.4 Hz,2H), 4.49 (d, J=6.0 Hz, 2H), 3.69 (m, 2H), 3.48 (m, 2H), 3.24 (m, 2H),2.77 (m, 1H), 1.86 (m,4H). MS (EI) for C₂₄H₂₅N₆O₂Br: 510 (MH⁺).

3-Amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.45 (m, 1H), 9.14 (m, 1H), 8.95 (s, 1H),8.67 (s, 1H), 8.35 (d, J=8.0 Hz, 1H), 7.90 (d, J=7.6 Hz, 1H), 7.58 (m,2H), 7.41 (m, 2H), 4.51 (d, J=8.0 Hz, 2H), 4.28 (m, 1H), 3.60 (m, 1H),3.24 (m, 2H), 2.77 (m, 2H), 1.89 (m, 2H), 1.81 (m, 2H). MS (EI) forC₂₄H₂₄BrFN₆O₂: 528 (MH⁺).

3-Amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.39 (t, J=5.6 Hz, 1H), 9.00 (m, 1H), 8.97(s, 1H), 8.85 (m, 1H), 8.68 (s, 1H), 8.36 (m, 1H), 7.93 (m, 1H), 7.64(m, 2H), 7.39 (m, 2H), 7.23 (m, 1H), 4.51 (d, J =6.0 Hz, 2H), 3.67 (m,1H), 3.50 (m, 1H), 3.25 (m, 2H), 3.14 (m, 1H), 2.77 (m, 2H), 1.91 (m,2H), 1.76 (m, 2H). MS (EI) for C₂₄H₂₅BrN₆O₂: 510 (MH⁺).

3-Amino-6-{3-[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide: ¹H NMR (400 MHz, d₆-DMSO): δ9.2 (t, 1H), 8.9 (s, 1H), 8.55 (s, 1H), 8.45 (d, 1H) 8.3 (d, 1H), 7.9(d, 1I1), 7.7-7.5 (m, 5H), 4.7 (d, 2H), 3.85 (m, 1H), 2.9 (m, 3H), 2.75(m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₅H₂₄N₆O₂F₄: 517 (MH⁺).

3-Amino-6-{3-[({[2-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.3 (t, 1H), 8.95 (s, 1H), 8.6 (d, 1H),8.55 (s, 1H), 8.3 (d, 1H), 8.0-7.5 (m, 6H), 7.4 (t, 1H), 4.6 (d, 2H),4.0 (m, 1H), 3.1-2.9 (m, 2H), 2.75 (t, 1H), 2.6 (t, 1H), 1.9-1.5 (m, 4).MS (EI) for C₂₅H₂₄N₆O₂F₄: 517 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3R)-pyrrolidin-3-ylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.83 (s, 1H), 8.72 (s, 1H), 8.43 (m, 1H),8.17 (m, 1H), 7.79 (m, 1H), 7.51 (m, 1H), 4.26 (m, 1H), 3.65 (m, 1H),3.58 (m, 2H), 3.47 (m, 3H), 3.37 (m, 3H1), 3.12 (m, 1H), 2.99 (m, 2H),2.68 (m, 1H), 2.13 (m, 1H), 2.00 (m, 2H), 1.83 (m, 3H). MS (EI) forC₂₂H₂₉N₇O₂: 424 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.80 (s, 1H), 8.58 (s, 1H), 8.24 (d, J=8.0Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.60 (t, J=8.0 Hz, 1H), 4.33 (m, 1H),3.75 (m, 1H), 3.63 (m, 2H), 3.50 (m, 2H), 3.20 (m, 2H), 3.04 (m, 2H),2.43 (m, 2H), 2.28 (m, 2H), 2.10 (m, 2H), 1.92 (m, 2H). MS (EI) forC₂₁H₂₇N₇O₂: 410 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-piperidin-1-ylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.80 (s, 1H), 8.64 (s, 1H), 8.24 (d, J=7.6Hz, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 4.33 (m, 1H),3.85 (m, 2H), 3.69 (m, 5H), 3.58 (m, 1H), 3.47 (m, 1H), 3.39 (m, 2H),3.24 (m, 2H), 3.02 (m, 2H), 2.10 (m, 2H), 2.00 (m, 2H), 1.86 (m, 4H). MS(EI) for C₂₄H₃₃N₇O₂: 452 (MH⁺).

3-Amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.76 (s, 1H), 8.48 (s, 1H), 8.18 (d, J=7.6Hz, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.76 (t, J=7.6 Hz, 1H), 7.26 (m, 4H),7.19 (m, 1H), 4.34 (m, 1H), 3.73 (m, 1H), 3.66 (m, 4H), 3.57 (m, 1H),3.48 (m, 1H), 3.36 (m, 2H), 3.15 (m, 1H), 3.02 (m, 1H), 2.95 (m, 2H),2.09 (m, 2H), 1.90 (m, 2H). MS (EI) for C₂₅H₂₈N₆O₂: 445 (MH⁺).

3-Amino-6-[3-({[2-(methyloxy)ethyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.76 (s, 1H), 8.48 (s, 1H), 8.18 (d, J=7.6Hz, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.76 (t, J=7.6 Hz, 1H), 4.33 (m, 1H),3.74 (m, 1H), 3.67 (m, 2H), 3.59 (m, 1H), 3.49 (m, 1H), 3.39 (m, 3H),3.34 (m, 2H), 3.16 (m, 1H), 3.02 (m, 1H), 2.10 (m, 2H), 1.90 (m, 211).MS (EI) for C₂₀H₂₆N₆O₃: 399 (MH⁺).

3-Amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.74 (s, 1H), 8.58 (m, 1H), 8.24-8.21 (m,1H), 7.90-7.88 (m, 1H), 7.62-7.59 (m, 1H), 7.39-7.32 (m, 4H), 4.60 (s,2H), 4.31-4.29 (m, 1H), 3.50-3.46 (m, 2H), 3.37-3.30 (m, 2H), 2.10-1.83(m, 4H). MS (EI) for C₂₄H₂₅N₆O₂I: 557 (MH⁺).

3-Amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.78 (s, 1H), 8.57 (m, 1H), 8.23-8.21 (m,1H), 7.92-7.89 (m, 1H), 7.62-7.59 (m, 1H), 7.37-7.30 (m, 4H), 4.60 (s,2H), 4.31-4.28 (m, 1H), 3.50-3.46 (m, 2H), 3.37-3.30 (m, 2H), 2.10-1.83(m, 4H). MS (EI) for C₂₄H₂₅N₆O₂Cl: 465(MH⁺).

3-Amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.8 (s, 1H), 9.2 (m, 1H), 9.03 (m, 1H),8.78 (s, 1H), 8.7 (d, 1H), 8.42 (s, if), 7.8 (m, 2H), 7.4 (m, 5H), 4.3(m, 1H), 3.7 (s, 2H), 3.3-3.2 (m, 3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS(EI) for C₂₄H₂₅N₆O₂Cl: 465 (MH⁺).

3-Amino-6-(3-{[(2,6-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.8 (s, 1H), 9.2 (m, 1H), 9.0 (m, 1H),8.78 (s, 1H), 8.7 (d, 1H), 8.4 (s, 1H), 7.85 (d, 1H), 7.72 (d, 1H), 7.5(t, 1H), 7.4 (m, 3H), 4.3 (m, 1H), 4.1 (s, 2H), 3.3-3.1 (m, 3H), 2.8 (m,1H), 2.0-1.7 (m, 4H). MS (EI) for C₂₄H₂₄N₆O₂Cl₂: 499 (MH⁺).

3-Amino-6-(3-{[(pentafluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 10.95 (s, 1H), 9.2 (m, 1H), 9.05 (m, 1H),8.78 (s, 1H), 8.65 (d, 1H), 8.4 (s, 1H), 7.85 (d, 1H), 7.75 (d, 1H), 7.4(t, 1H), 4.3 (m, 1H), 3.96 (s, 2H), 3.3-3.1 (m, 3H), 2.8 (m, 1H),2.0-1.7 (m, 4H). MS (EI) for C₂₄H₂₁N₆O₂F₅: 521 (MH⁺).

3-Amino-6-(3-{[(2-chloro-4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.7 (s, 1H), 9.2 (m, 1H), 9.05 (m, 1H),8.78 (s, 1H), 8.7 (d, 1H), 8.4 (s, 1H), 7.85 (d, 1H), 7.75 (d, 1H), 7.5(t, 1H), 7.45 (m, 2H), 7.25 (m, 1H), 4.3 (m, 1H), 3.9 (s, 2H), 3.3-3.1(m, 3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS (EI) for C₂₄H₂₄N₆O₂FCl: 483(MH⁺).

3-Amino-6-[3-({[4-(methylthio)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.7 (s, 1H), 9.2 (m, 1H), 9.0 (m, 1H),8.78 (s, 1H), 8.7 (d, 1H), 8.4 (s, 1H), 7.8 (d, 2H), 7.4 (m, 3H), 7.2(d, 2H), 4.3 (m, 1H), 3.7 (s, 2H), 3.3-3.1 (m, 3H), 2.8 (m, 1H), 2.45(s, 3H), 2.0-1.7 (m, 4H). MS (EI) for C₂₅H₂₈N₆O₂S: 477 (MH⁺).

3-Amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.8 (s, 1H), 9.25 (m, 1H), 9.1 (m, 1H),8.78 (s, 1H), 8.7 (d, 1H), 8.43 (s, 1H), 7.85 (d, 1H), 7.8 (d, 1H), 7.6(s, 1H), 7.5 (t, 1H), 7.4 (m, 2H), 4. 3(m, 1H), 3.9 (s, 2H), 3.3-3.1 (m,3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS (EI) for C₂₄H₂₄N₆O₂Cl₂: 499 (MH⁺).

3-Amino-6-[3-({[4-(4-chlorophenyl)-2-thienyl]carbonyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.85 (s, 1H), 9.2-9.1 (m, 2H), 9.0-8.8 (m,4H), 8.27 (s, 1H), 8.05 (d, 1H), 7.9-7.8 (m, 3H), 7.57 (d, 2H), 7.45 (t,1H), 4.4 (m, 1H), 3.3-3.1 (m, 3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS (EI)for C₂₇H₂₅N₆O₂SCl: 533 (MH⁺).

3-Amino-6-(3-{[(2,4-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.7 (s, 1H), 9.1 (m, 1H), 8.95 (m, 1H),8.75 (s, 1H), 8.67 (d, 1H), 8.4 (s, 1H), 7.82 (d, 1H), 7.72 (d, 1H), 7.5(q, 1H), 7.4 (t, 1H), 7.25 (m, 1), 7.1 (m, 1H), 4.5 (s, 1H), 4.3 (m,1H), 3.8 (s, 2H), 3.2 (m, 3H), 2.75 (m, 1H), 1.95-1.7 (m, 4H). MS (EI)for C₂₄H₂₄N₆O₂F₂: 483 (MH⁺).

3-Amino-6-(3-{[(2-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.7 (s, 1H), 9.15 (m, 1H), 9.0 (m, 1H),8.75 (s, 1H), 8.7 (d, 1H), 8.4 (s, 1H), 7.8 (d, 1H), 7.75 (d, 1H),7.5-7.1 (m, 5H), 4.3 (m, 1H), 3.8 (s, 2H), 3.2 (m, 3H), 2.75 (s, 1H),1.95-1.7 (m, 4H). MS (EI) for C₂₄H₂₅N₆O₂F: 449 (MH⁺).

3-Amino-6-{3-[({5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2-yl}carbonyl)amino]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.75 (s. 1H), 9.05 (m, 1H), 8.9 (m, 1H1),8.85 (s, 1H), 8.75 (d, 1H), 8.6 (s, 1H), 8.5 (s, 1H), 7.9 (t, 3H), 7.8(m, 2H), 7.5 (m, 2H), 4.3 (m, 1H), 3.35 (m, 3H), 2.75 (q, 1H), 1.9 (m,3H), 1.75 (m, 1H). MS (EI) for C₂₈H₂₄N₆O₃F₃Cl: 585 (MH⁺).

3-Amino-6-[3-({[4-(dimethylamino)naphthalen-1-yl]carbonyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.7 (s, 1H), 9.2 (m, 1H), 9.05 (m, 1H),8.8 (s, 1H), 8.7 (d, 1H), 8.55 (s, 1H), 8.3 (m, 2H), 7.9 (t, 2H), 7.8(d, 1H), 7.6 (m, 2H), 7.5 (t, 1H), 4.3 (m 1H), 3.3-3.1 (m, 3H), 3.0 (s,6H), 2.75 (m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₉H₃₁N₇O₂: 510 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4-(1,2,3-thiadiazol-5-yl)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.7 (s, 1H), 9.85 (s, 1H), 9.15 (m, 1H),8.95 (m, 1H), 8.8 (d, 2H), 8.67 (s, 1H), 8.3 (q, 4H), 8.0 (d, 1H), 7.9(d, 1H), 7.5 (t, 1H), 4.3 (m, 1H), 3.25 (m, 3H), 2.75 (m, 1H), 1.95-1.7(m, 4H). MS (EI) for C₂₅H₂₄N₈O₂S: 501 (MH⁺.

3-Amino-6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.5 (s, 1H), 9.25 (m, 1H), 9.1 (m, 1H),8.8 (m, 2H), 8.7 (s, 1H), 7.95 (d, 1H), 7.85 (d, 1H), 7.45 (t, 1H), 7.2(s, 1H), 5.75 (s, 1H), 4.3 (m, 1H), 3.25 (m, 3H), 2.75 (m, 1H), 1.95-1.7(m, 4H). MS (EI) for C₂₂H₂₆N₈O₂: 435 (MH⁺).

3-Amino-6-(3-{[(4-bromo-2-fluorophenyl)carbonyl]aminophenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide: ¹H NMR (400 MHz,d₆-DMSO): δ 10.7(s, 1H), 9.1(m, 1H), 8.9(m, 1H), 8.78(s, 1H), 8.7(d,1H), 8.4(s, 1H), 7.9(d, 1H), 7.8(m, 2H), 7.7(d, 1H), 7.58(d, 1H), 7.5(t,1H), 4.3(m, 1H), 3.3-3.1(m, 3H), 2.8(m, 1H), 2.0-1.7(m, 4H). MS (EI) forC₂₃H₂₂N₆O₂FBr: 515 (MH⁺).

N-[3-(5-Amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]quinoline-3-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 11.15 (s, 1H), 9.65 (s, 1H), 9.4 (s, 1H),9.18 (m, 1H), 8.98 (m, 1H), 8.83 (s, 1H), 8.8 (m, 2H), 8.25 (d, 1H), 8.2(d, 1H), 8.1 (d, 1H), 8.0 (t, 1H), 7.9 (d, 1H), 7.8 (t, 1H), 7.5 (t,1H), 4.3 (m, 1H), 3.3-3.2 (m, 3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS (EI)for C₂₆H25N₇O₂: 468 (MH⁺).

3-Amino-6-[3-({[6-(methyloxy)-1-benzofuran-3-yl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.6 (s, 1H), 8.9 (m, 1H), 8.8 (m, 1H),8.78 (s, 1H), 8.7 (d, 1H), 8.35 (s, 1H), 7.8 (m, 2H), 7.73 (d, 1H), 7.6(d, 1H), 7.4 (t, 1H), 7.2 (s, 1H), 6.9 (d, 1H), 4.3 (m, 1H), 3.8 (s,2H), 3.78 (d, 2H), 3.3-3.1 (m, 3H), 2.8 (m, 1H), 2.0-1.7 (m, 4H). MS(EI) for C₂₇H₂₈N₆O₄: 501 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.5 (s, 1H), 9.05 (m, 1H), 8.9 (m, 1H),8.67 (s, 1H), 8.6 (d, 1H), 8.2 (s, 1H), 7.85 (d, 1H), 7.75 (d, 2H),7.7-7.5 (m, 7H), 7.4 (t, 1H), 4.3 (m, 1H), 4.05 (s, 1H), 3.25 (m, 2H),3.05 (m, 1H), 2.75 (m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₃₀H₂₇N₆O₂F₃:561 (MH⁺).

3-Amino-6-[3-({[3,5-bis(trifluoromethyl)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 0.8 (s, 1H), 9.05 (m, 1H), 8.9 (m, 1H),8.72 (s, 1H), 8.52 (d, 1H), 8.35 (s, 1H), 8.1 (s, 2H), 8.0 (s, 1H), 7.8(d, 1H), 7.7 (d, 2H), 7.4 (t, 1H), 4.3 (m, 1H), 4.0 (s, 2H), 3.3-3.15(m, 3H), 2.75 (m, 1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₆H₂₄N₆O₂F₆: 567(MH⁺).

3-Amino-6-{3-[({[4-(4-methylpiperazin-1-yl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 8.60 (s, 1H), 8.23 (m, 1H),7.90 (m, 1H), 7.61 (m, 1H), 7.36 (m, 2H), 7.06 (m, 2H), 4.56 (s, 2H),4.39-4.37 (m, 1H), 3.86-3.83 (m, 2H), 3.67-3.61 (m, 2H), 3.51-3.48 (m,2H), 3.38-3.35 (m, 1H), 3.31-2.97 (m, 8H), 2.09-1.96 (m, 4H). MS (EI)for C₂₉H₃₆N₈O₂: 529 (MH⁺).

3-Amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.74 (s, 1H), 8.50 (m, 1H), 8.21-8.19 (m,1H), 7.81-7.78 (m, 1H), 7.59-7.55 (m, 1H), 7.30-7.26 (m, 2H), 7.03-6.99(m, 2H), 4.35 (m, 1H), 3.69-2.93 (m, 8H), 2.11-1.91 (m, 4H). MS (EI) forC₂₅H₂₇N₆O₂F: 463 (MH⁺).

3-Amino-6-(3-{[(2-morpholin-4-ylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.80 (s, 1H), 8.67 (s, 1H), 8.24 (m, 1H),7.95 (m, 1H), 7.63-7.59 (m, 1H), 4.37-4.36 (m, 1H), 4.12-4.08 (m, 2H),3.89-3.84 (m, 4H), 3.75-3.66 (m, 2H), 3.49-3.03 (m, 8H), 2.12-1.91 (m,4H). MS (EI) for C₂₃H₃₁N₇O₃: 454 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2R)-pyrrolidin-2-ylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.77 (s, 1H), 8.61 (s, 1H), 8.25-8.23 (m,1H), 7.93-7.91 (m, 1H), 7.63-7.61 (m, 1H), 4.37 (m, 1H), 3.57-2.77 (m,1H), 2.24-1.86 (m, 6H). MS (EI) for C₂₂H₂₉N₇O₂: 424 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2S)-pyrrolidin-2-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.77 (s, 1H), 8.61 (s, 1H), 8.25-8.23 (m,1H), 7.92-7.89 (m, 1H), 7.64-7.62 (m, 1H), 4.78-4.75 (m, 1H), 4.39-4.37(m, 1H), 3.57-2.77 (m, 8H), 2.44-1.93 (m, 6H). MS (EI) for C₂₁H₂₇N₇O₂:410 (MH⁺).

3-Amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.73 (s, 1H), 8.53 (s, 1H), 8.24-8.22 (m,1H), 7.88-7.86 (m, 1H), 7.62-7.58 (m, 1H), 4.99-4.89 (m, 2H), 3.59-3.49(m, 1H), 3.39-3.30 (m, 1H) 3.24-3.21 (m, 1H) 3.09-3.01 (m, 1H),2.37-1.67 (m, 1H). MS (EI) for C₂₂H₂₇N₆O₂: 409 (MH⁺).

3-Amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 M , d₄-MeOH): δ 8.89 (s, 1H), 8.57 (m, 1H), 8.18 (m, 1H),8.05 (m, 1H), 7.82 (m, 1H), 7.78 (m, 1H), 7.42-7.24 (m, 4H), 4.62 (m,3H), 4.27 (m, 1H), 3.42-2.92 (m, 4H), 2.18-1.84 (m, 4H), 1.27 (s, 9H).MS (EI) for C₂₈H₃₄N₆O₂: 487 (MH⁺).

3-Amino-6-[3-({[(2,4-dichloro-6-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.78 (s, 1H), 8.65 (m, 1H), 8.18 (m, 1H),7.82 (m, 1H), 7.57 (m, 1H), 7.39-7.23 (m, 2H), 4.68 (m, 3H), 4.26 (m,1H), 3.42-2.92 (m, 4H), 2.44 (s, 3H), 2.19-1.86 (m, 4H). MS (EI) forC₂₅H₂₆N₆O₂Cl₂: 513 (MH⁺).

3-Amino-6-[3-({[(3,5dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.82 (s, 1H), 8.63 (m, 1H), 8.57 (m, 1H),8.22 (m, 1H), 7.59 (m, 1H), 7.26 (s, 3EI), 4.68 (m, 3H), 4.26 (m, 1H),3.47-2.99 (m, 4H), 2.15-1.82 (m, 4H). MS (EI) for C₂₄H₂₄N₆O₂Cl₂: 499(MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.6 (s, 1H), 9.55 (t, 1H), 9.2 (m, 1H),9.0-8.9 (m, 3H), 8.7 (s, 1H), 8.35 (d, 1H), 8.1 (d, 2H), 7.95 (d, 1H),7.6-7.5 (m, 3H), 4.6 (d, 2H), 4.3 (m, 1H), 3.3-3.1 (m, 3H), 2.75 (m,1H), 1.95-1.7 (m, 4H). MS (EI) for C₂₆H₂₆N₈O₂S: 515 (MH⁺).

3-Amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.0 (s, 2H), 9.55 (s, 2H), 9.15 (d, 1H),8.92 (s, 1H), 8.12 (d, 1H), 7.9 (d, 1H), 7.6-7.45 (m, 4H), 7.35-7.25 (m,3H), 4.85-4.8 (m, 2H), 4.3 (s, 2H), 3.4 (m, 4H), 3.2 (m, 2H), 2.9 (m,1H), 2.45 (m, 2H), 2.3-2.15 (m, 2H). MS (EI) for C₂₅H₂₈N₆O: 429 (MH⁺).

3-Amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.2 (s, 1H), 9.6 (s, 2H), 9.3 (m, 1H), 9.1(d, 1H), 8.9 (d, 2H), 8.15 (d, 1H), 7.9 (d, 1H), 7.58 (d, 1H), 7.45 (t,1H), 7.3-7.2 (m, 3H), 4.8 (m, 2H), 4.6 (m, 1H), 4.45 (m, 2H), 3.55 (m,3H), 3.25-3.1 (m, 2H), 3.0 (d, 1H), 2.3-2.15 (m, 2H). MS (EI) forC₂₅H₂₈N₆O₂: 445. (MH⁺).

3-Amino-N-[(3S)-pyrrolidin-3-yl]-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-ylamino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CDCl₃): δ 8.63 (s, 1H), 8.24 (d, 1H), 7.75 (s, 1H),7.72-7.75 (m, 1H), 7.38-7.46 (m, 3H), 7.14-7.18 (m, 2H), 7.08-7.11 (m,1H), 4.52-4.56 (m, 1H), 3.94-4.06 (m, 2H), 3.09 (t, 1H), 2.96-3.03 (m,2H), 2.68-2.88 (m, 5H), 2.21-2.29 (m, 1H), 1.94-2.06 (m, 3H1), 1.74-1.86(m, 2H). MS (EI) for C₂₆H₃₀N₆O: 443 (MH⁺).

3-Amino-6-(3-hydroxyphenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.36 (br s, 2H), 8.80 (d, 1H), 8.75 (s,1H), 7.57-7.53 (m, 2H), 7.23 (t, 1H), 6.78 (d, 1H), 4.64-4.57 (m, 2H),4.20 (br s, 1H), 3.44-3.34 (m, 2H), 3.29-3.17 (m, 2H), 2.28-2.19 (m,1H), 2.10-2.03 (m, 1H). MS (EI) for C₁₅H₁₇N₇O₂: 300 (MH⁺).

3-Amino-6-(3-hydroxyphenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.54 (br s, 1H), 8.93 (m, 1H), 8.82-8.79(m, 1H), 7.75 (s, 1H), 8.62 (d, 1H), 7.60 (br s, 1H), 7.59-7.46 (m, 2H),7.24 (t, 1H), 6.81 (d, 1H), 4.21 (br s, 1H), 3.27-3.20 (m, 2H), 3.03 (q,1H), 2.76-2.74 (m, 1H), 1.89-1.87 (m, 2H), 1.76-1.72 (m, 2H). MS (EI)for C₁₆H₁₉N₅O₂: 314 (MH⁺).

5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4-piperidin-3-yl-1,3-thiazol-2-yl)pyrazin-2-amine:¹H NMR (400 MHz, d₆-DMSO): δ 9.4 (t, 2H), 8.9 (d, 1H), 8.8 (s, 1H), 8.63(d, 1H), 8.15 (s, 1H), 8.05 (d, 1H), 7.9 (m, 1H), 7.67 (m, 2H), 7.6-7.5(m, 2H), 7.4-7.25 (m, 3H), 4.85 (m, 1H), 4.3 (d, 2H), 3.6 (d, 1H),3.4-3.0 (m, 4H), 2.9 (t, 2H), 2.4-2.0 (m, 2H),20-1.7 (m, 3H). MS (EI)for C₂₈H₃₀N₆S: 483 (MH⁺).

1,1-Dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]phenyl}pyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate:¹H NMR (400 MHz, CDCl₃): δ 8.4 (s, 1H), 8.2 (m, 1H), 7.80 (m, 2H), 7.4(m, 1H), 4.6 (s, 2H), 4.1 (m, 1H), 3.4 (m, 4H), 1.8 (m, 4H), 1.5-1.6 (m,18H). MS (EI) for C₂₇H₃₈N₆O₅: 527 (MH⁺).

3-Amino-6-[3-(aminomethyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.4 (s, 1H), 8.2 (m, 1H), 7.80 (m, 2H), 7.4(m, 1H), 4.6 (s, 2H), 4.1 (m, 1H), 3.4 (m, 4H), 1.8 (m, 4H). MS (EI) forC₁₇H₂₂N₆O: 327 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2-(2-thienyl)-1,3-thiazol-4-yl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.4 (s, 1H), 8.2 (m, 1H), 7.80 (m, 2H), 7.6(s, 1H), 7.4 (m, 3H), 7.2 (m, 1H), 4.6 (s, 2H), 4.1 (m, 1H), 3.4 (m,4H), 1.8 (m, 4H). MS (EI) for C₂₅H₂₅N₇O₂S₂: 520 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[5-(2-thienyl)pyridin-3-yl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): 6 8.4 (s, 1H), 8.2 (m, 1H), 7.80 (m, 2H), 7.6(s, 1H), 7.4 (m, 3H), 7.3 (m, 2H), 7.2 (m, 1H) 4.6 (s, 2H), 4.1 (m, 1H),3.4 (m, 4H), 1.8 (m, 4H). MS (EI) for C₂₇H₂₇N₇O₂S: 514 (MH⁺).

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (m, 1H), 8.50 (d, 1H), 8.40-8.10 (m,4H), 7.60-7.40 (m, 2H), 4.10 (m, 2H), 3.90-3.60 (m, 3H), 3.30-3.00 (m,2H), 1.90-1.60 (m, 4H), 1.40 (s, 9H). MS (EI) for C₂₂H₃₀N₆O₃: 427 (MH⁺).

3-Amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MH, d₄-MeOH): δ 8.72 (s, 1H), 8.02 (s, 1H), 7.90-7.95 (m,3H), 7.40-7.46 (m, 2H), 7.21 (t, 2H), 4.66 (m, 2H), 3.37-3.73 (m, 2H),2.91-3.13 (m, 3H), 1.76-2.06 (m, 4H). MS (EI) for C₂₄H₂₅N₆O₂F: 449(MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 9.14-9.20 (m, 1H), 8.72 (s, 1H), 8.58-8.59(m, 1H), 8.03 (s, 1H), 7.97-7.99 (m, 2H), 7.91-7.93 (m, 1H), 7.41-7.48(m, 1H), 7.38-7.39 (m, 1H), 4.62-4.71 (m, 2H), 4.27 (s, 1H), 3.47-3.50(m, 1H), 3.32-3.49 (m, 1H), 3.06-3.12 (m, 2H), 2.94-2.99 (m, 1H),2.03-2.06 (m, 2H), 1.79-1.87 (m, 2H). MS (EI) for C₂₅H₂₅N₆O₃F₃: 515(MH⁺).

3-Amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 8.02 (s, 1H), 7.90-7.92 (m,2H), 7.85-7.87 (m, 2H), 7.44-7.51 (m, 3H), 7.38-7.39 (m, 1H), 4.64-4.66(m, 2H), 4.27 (s, 1H), 3.46-3.73 (m, 2H), 2.96-3.09 (m, 3H), 1.77-2.05(m, 4H). MS (EI) for C₂₄H₂₅N₆O₂Cl: 465 (MH⁺).

3-Amino-6-[3-({[(4-bromophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 8.01 (s, 1H), 7.93-7.89 (m,1H), 7.81-7.76 (m, 2H), 7.68-7.63 (m, 2H), 7.48-7.42 (m, 1H), 7.41-7.36(m, 1H), 4.71-4.59 (m, 2H), 4.35-4.20 (m, 1H), 3.51-3.44 (m, 1H),3.39-3.30 (m, 1H), 3.11-3.02 (m, 1H), 3.00-2.91 (m, 1H), 2.10-1.96 (m,2H), 1.94-1.67 (m, 2H). MS (EI) for C₂₄H₂₅N₆O₂Br: 508 (MH⁺).

3-Amino-6-(3-{[(naphthalen-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.73 (s, 1H), 8.45 (s, 1H), 8.07 (s, 1H),8.02-7.88 (m, 5H), 7.64-7.54 (m, 2H), 7.51-7.40 (m, 2H), 4.81-4.65 (m,2H), 4.25-4.12 (m, 1H), 3.49-3.40 (m, 1H), 3.30-3.22 (m, 1H1), 3.02-2.93(m, 1H), 2.84-2.74 (m, 1H), 1.95-1.65 (m, 3H), 1.63-1.50 (m, 1H). MS(EI) for C₂₈H₂₈N₆O₂: 481 (MH⁺).

3-Amino-6-{3-[({[4-(dimethylamino)phenyl]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.70 (s, 1H), 8.55 (d, 1H), 8.00 (s, 1H),7.90-7.70 (m, 3H), 7.50-7.30 (m, 2H), 6.80-6.70 (m, 2H), 4.65 (m, 2H),3.50-2.80 (m, 10H), 2.00-1.60 (m, 4H). MS (EI) for C₂₆H₃₁N₇O₂: 474(MH⁺).

3-Amino-6-{3-[({[4-(methyloxy)phenyl]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide: ¹HNMR (400 MHz, d₄-MeOH): δ 8.70 (s, 1H), 8.55 (d, 1H), 8.05 (s, 1H),8.00-7.85 (m, 4H), 7.50-7.40 (m, 2H), 7.00 (m, 2H), 4.65 (m, 2H), 4.25(m, 1H), 3.80 (s, 3H), 3.50 (m, 1H), 3.10 (m, 1H), 2.95 (m, 1H), 2.00(m, 2H), 1.80 (m, 2H). MS (EI) for C₂₅H₂₈N₆O₃: 461(MH⁺).

3-Amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.70 (s, 1H), 8.55 (d, 1H), 8.05 (s, 1H),8.00-7.85 (m, 3H), 7.80-7.60 (m, 4H), 7.50-7.30 (m, 5SE), 4.65 (m, 2H),4.25 (m, 1H), 3.50 (m, 1H), 3.10 (m, 1H), 2.95 (m, 1H), 2.00 (m, 2H),1.80 (m, 2H). MS (EI) for C₃₀H₃₀N₆O₂: 507 (MH⁺).

3-Amino-6-(3-{[(furan-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.70 (s, 1H), 8.55 (d, 1H), 8.10 (s, 1H),8.00 (s, 1H), 7.95 (m, 1H), 7.60 (m, 1H), 7.45-7.25 (m, 2H), 6.80 (m,1H), 4.65 (m, 2H), 4.25 (m, 1H), 3.50 (m, 1H), 2.95 (m, 3H), 2.00 (m,2H), 1.80 (m, 2H). MS (EI) for C₂₂H₂₄N₆O₃: 421 (MH⁺).

3-Amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylcarbonyl)amino]methyl)phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 8.01 (s, 1H), 7.92-7.87 (m,1H), 7.76 (s, 1H), 7.71-7.66 (m, 1H), 7.48-7.41 (m, 1H), 7.40-7.35 (m,1H), 6.81-6.76 (m, 1H), 4.67-4.57 (m, 4H), 4.33-4.20 (m, 1H), 3.52-3.42(m, 1H), 3.40-3.20 (m, 3H), 3.11-3.02 (m, 1H), 3.00-2.90 (m, 1H),2.08-1.97 (m, 2H), 1.90-1.68 (m, 2H). MS (EI) for C₂₆H₂₈N₆O₃: 473 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-thienylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.70 (s, 1H), 8.55,d, 1H), 8.10 (s, 1H),8.00 (s, 1H), 7.95 (m, 1H), 7.60, 7.35 (m, 5H), 4.65 (m, 2H), 4.25 (m,1H), 3.50 (m, 1H), 2.95 (m, 3H), 2.00 (m, 2H), 1.80 (m, 2H). MS (EI) forC₂₂H₂₄N₆O₂S: 437 (MH⁺).

3-Amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.80 (m, 1H), 8.70 (m, 1H), 7.95-7.75 (m,2H), 7.40 (m, 1H), 7.20 (m, 1H), 7.00 (m, 1H), 6.95-6.85 (m, 3H), 4.85(m, 1H), 4.60 (m, 1H), 4.50-4.25 (m, 4H), 3.50 (m, 1H), 3.35 (m, 1H),3.10 (m, 1H), 2.95 (m, 1H), 2.10 (m, 21), 1.95 (m, 2H). MS (EI) forC₂₆H₂₈N₆O₄: 489 (MH⁺).

N-[(3-{5-Amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-(4-bromophenyl)urea:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 7.99 (s, 1H), 7.92-7.86 (m,1H), 7.48-7.42 (m, 1H), 7.41-7.32 (m, 5H), 4.57-4.38 (m, 2H), 4.34-4.20(m, 1H), 3.50-3.42 (m, 1H), 3.37-3.30 (m, 1H), 3.11-3.00 (m, 1H),2.95-2.82 (m, 1H), 2.07-1.91 (m, 2H), 1.89-1.66 (m, 2H). MS (EI) forC₂₄H₂₆N₇O₂Br: 523 (MH⁺).

N-[(3-{5-Amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-naphthalen-2-ylurea: ¹H NMR (400 MHz, d₄-MeOH): δ8.62 (s, 1H), 7.95-7.87 (m, 2H), 7.81-7.75 (m, 1H), 7.70-7.59 (m, 3H),7.39-7.20 (m, 5H), 4.55-4.33 (m, 2H), 4.16-4.04 (m, 1H), 3.35-3.27 (m,1H), 3.10-3.01 (m, 1H), 2.92-2.83 (m, 1H), 2.61-2.51 (m, 1H), 1.86-1.76(m, 1H), 1.65-1.46 (m, 3H). MS (EI) for C₂₈H₂₉N₇O₂: 496 (MH⁺).

3-Amino-6-[3-({[(biphenyl-4-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.74 (s, 1H), 8.03 (s, 1H), 7.92-7.86 (m,1H), 7.61-7.34 (m, 10H), 7.32-7.25 (m, 1H), 4.61-4.42 (m, 2H), 4.32-4.18(m, 1H), 3.49-3.41 (m, 1H), 3.30-3.21 (m, 1H), 3.08-2.99 (m, 1H),2.90-2.78 (m, 1H), 2.07-1.67 (m, 4H). MS (EI) for C₃₀H₃₁N₇O₂: 522 (MH⁺).

3-Amino-6-{3-[({[(2,4-difluorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.63 (s, 1H), 7.89 (s, 1H), 7.78-7.83 (m,2H), 7.36 (t, 1H), 7.26-7.28 (m, 1H), 6.88-6.93 (m, 1H), 6.78-6.83 (m,1H), 4.34-4.43 (m, 2H), 4.13-4.25 (m, 1H), 3.36-3.40 (m, 1H), 3.24-3.27(m, 1H), 2.97-3.03 (m, 1H), 2.79-2.89 (m, 1H), 1.92-1.98 (m, 2H),1.71-1.75 (m, 2H). MS (EI) for C₂₄H₂₅N₇O₂F₂: 482 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({2-[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.76 (s, 1H), 8.13-8.15 (m, 1H), 7.99 (s,1H), 7.90-7.92 (d, 1H), 7.46 (t, 1H), 7.36-7.38 (m, 1H), 7.26-7.30 (m,2H), 7.04-7.09 (m, 1H), 4.44-4.55 (m, 2H), 4.02-4.03 (m, 1H), 3.45-3.48(m, 1H), 3.07-3.13 (m, 2H), 2.92-2.95 (m, 1H), 1.77-2.05 (m, 4H). MS (E)for C₂₅H₂₆N₇O₃F₃: 530 (MH⁺).

3-Amino-6-(3-{[({[2-(methylthio)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.64 (s, 1H), 7.93 (s, 1H), 7.80 (d, 1H),7.69-7.71 (m, 1H), 7.26-7.38 (m, 3H), 7.09-7.14 (m, 1H), 6.96-6.98 (m,1H), 4.34-4.46 (m, 2H), 4.09-4.13 (m, 1H), 3.31-3.38 (m, 1H), 2.90-2.98(m, 2H), 2.78-2.83 (m, 1H), 2.80 (s, 3H), 1.84-1.94 (m, 2H), 1.66-1.73(m, 2H). MS (EI) for C₂₅H₂₉N₇O₂S: 492 (MH⁺).

3-Amino-6-{3-[({[(3-bromo-5-methylphenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.73 (s, 1H), 8.01 (s, 1H), 7.89-7.91 (m,1H), 7.54-7.57 (m, 1H), 7.45 (t, 1H), 7.34-7.37 (m, 2H), 7.26-7.29 (m,1H), 4.42-4.54 (m, 2H), 4.21-4.30 (m, 1H), 3.45-3.48 (m, 1H), 2.86-3.15(m, 3H), 2.21 (s, 3H), 1.99-2.02 (m, 2H), 1.78-1.82 (m, 2H). MS (EI) forC₂₅H₂₈N₇O₂Br: 539 (MH⁺).

3-Amino-6-{3-[({[(2-bromophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.64 (s, 1H), 7.92 (s, 1H), 7.81-7.88 (m,2H), 7.45-7.47 (m, 1H), 7.39 (t, 1H), 7.27-7.29 (m, 1H), 7.18-7.22 (m,1H), 6.84-6.88 (m, 1H), 4.81 (s, 1H), 4.35-4.46 (m, 2H), 4.12-4.23 (m,1H), 3.35-3.39 (m, 1H), 2.94-2.99 (m, 1H), 2.78-2.82 (m, 1H), 1.67-1.96(m, 4H). MS (EI) for C₂₄H₂₆N₇O₂Br: 525 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4-[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.73 (s, 1H), 7.99 (s, 1H), 7.89-7.91 (m,1H), 7.44-7.49 (m, 3H), 7.40-7.38 (m, 1H), 7.16-7.18 (m, 2H), 4.43-4.55(m, 2H), 4.21-4.32 (m, 1H), 3.46-3.48 (m, 1H), 3.29-3.34 (m, 1H),3.05-3.13 (m, 1H), 2.86-2.94 (m, 1H), 1.79-2.03 (m, 4H). MS (EI) forC₂₅H₂₆N₇O₃F₃: 530 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.73 (s, 1H), 8.00 (s, 1H), 7.89-7.91 (m,1H), 7.53-7.60 (m, 4H), 7.44-7.47 (m, 1H), 7.36-7.38 (m, 1H), 4.44-4.56(m, 2H), 4.22-4.33 (m, 1H), 3.43-3.50 (m, 1H), 3.04-3.12 (m, 2H),2.83-2.94 (m, 1H), 1.73-2.08 (m, 4H). MS (EI) for C₂₅H₂₆N₇O₂F₃: 514(MH⁺).

3-Amino-6-[3-({[(2,3-dihydro-1,4-benzodioxin-6-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.73 (s, 1H), 8.01 (s, 1H), 7.90-7.85 (m,1H), 7.47-7.41 (m, 1H), 7.37-7.32 (m, 1H), 7.02-6.98 (m, 1H), 6.73-6.70(m, 2H), 4.55-4.37 (m, 2H), 4.33-4.22 (m, 1H), 4.23-4.15 (m, 4H),3.50-3.43 (m, 1H), 3.36-3.30 (m, 1H), 3.11-3.02 (m, 1H), 2.96-2.85 (m,1H), 2.09-1.71 (m, 4H). MS (EI) for C₂₆H₂₉N₇O₄: 504 (MH⁺).

3-Amino-6-[3-({[(1,3-benzodioxol-5-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.71 (s, 1H), 8.01 (s, 1H), 7.90-7.85 (m,1H), 7.47-7.41 (m, 1H), 7.37-7.32 (m, 1H), 7.10-7.07 (m, 1H), 6.74-6.64(m, 2H), 5.90 (s, 2H), 4.54-4.38 (m, 2H), 4.33-4.22 (m, 1H), 3.50-3.43(m, 1H), 3.37-3.31 (m, 1H), 3.12-3.03 (m, 1H), 2.96-2.86 (m, 1H),2.08-1.96 (m, 2H), 1.89-1.72 (m, 2H). MS (EI) for C₂₅H₂₇N₇O₄: 490 (MH⁺).

3-Amino-6-(3-{[({[4-(methyloxy)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 8.00 (s, 1H), 7.91-7.86 (m,1H), 7.47-7.41 (m, 1H), 7.38-7.33 (m, 1H), 7.29-7.24 (m, 2H), 6.88-6.82(m, 2H), 4.55-4.39 (m, 2H), 4.33-4.19 (m, 1H), 3.75 (s, 3H), 3.50-3.41(m, 1H), 3.34-3.26 (m, 1H), 3.10-3.00 (m, 1H), 2.93-2.82 (m, 1H),2.08-1.91 (m, 2H), 1.89-1.78 (m, 2H). MS (EI) for C₂₅H₂₉N₇O₃: 476 (MH⁺).

3-Amino-6-{3-[({[(4-fluorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 7.99 (s, 1H), 7.92-7.87 (m,1H), 7.49-7.41 (m, 1H), 7.40-7.33 (m, 3H), 7.04-6.96 (m, 2H), 4.55-4.44(m, 2H), 4.32-4.22 (m, 1H), 3.50-3.43 (m, 1H), 3.36-3.29 (m, 1H),3.12-3.03 (m, 1H), 2.96-2.86 (m, 1H), 2.08-1.95 (m, 2H), 1.90-1.73 (m,2H). MS (EI) for C₄H₂₆N₇O₂F: 464 (MH⁺).

3-Amino-6-(3-{[({[4-(dimethylamino)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72 (s, 1H), 7.99-7.90 (m, 2H), 7.65-7.58(m, 2EI), 7.54-7.42 (m, 3H), 7.39-7.34 (m, 1H), 4.49 (s, 2H), 4.36-4.24(m, 1H), 3.53-3.44 (m, 1H), 3.39-3.30 (m, 1H), 3.15-3.05 (m, 1H),3.04-2.90 (m, 1H), 2.15-1.97 (m, 2H), 1.95-1.82 (m, 2H). MS (EI) forC₂₆H₃₂N₈O₂: 489 (MH⁺).

3-Amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.65 (s, 1H), 7.93 (s, 1H), 7.89-7.83 (m,1H), 7.63-7.55 (m, 2H), 7.39-7.33 (m, 1H), 7.24-7.19 (m, 1H), 6.77-6.72(m, 1H), 4.62-4.53 (m, 2H), 4.39-4.24 (m, 1H), 4.15 (s, 2H), 3.54-3.46(m, 1H), 3.39-3.31 (m, 1H), 3.21-3.10 (m, 3H), 3.06-2.92 (m, 1H),2.19-2.03 (m, 2H), 1.96-1.81 (m, 2H). MS (EI) for C₂₅H₂₈N₆O₄S: 509(MH⁺).

3-Amino-6-(3-{[(3,4-dihydro-2H-1,5-benzodioxepin-7-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.67 (s, 1H), 7.95 (s, 1H), 7.88-7.83 (m,1H), 7.39-7.32 (m, 3H), 7.24-7.19 (m, 1H), 6.98-6.93 (m, 1H), 4.38-4.27(m, 1H), 4.21-4.11 (m, 6H), 3.55-3.46 (m, 1H), 3.40-3.31 (m, 1H),3.19-3.08 (m, 1H), 3.06-2.94 (m, 1H), 2.22-2.02 (m, 4H), 1.98-1.81 (m,2H). MS (EI) for C₂₆H₃₀N₆O₅S: 539 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(quinolin-7-ylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.98-8.95 (m, 1H), 8.46 (s, 1H), 8.28-8.23(m, 2H), 8.04-7.99 (m, 1H), 7.75 (s, 1H), 7.63-7.46 (m, 3H), 7.10-6.98(m, 2H), 4.39-4.26 (m, 1H), 4.26 (s, 2H), 3.55-3.48 (m, 1H), 3.39-3.31(m, 1H), 3.19-3.10 (m, 1H), 3.04-2.92 (m, 1H), 2.21-2.02 (m, 2H),2.00-1.82 (m, 2H). MS (EI) for C₂₆H₂₇N₇O₃S: 518 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.57 (s, 1H), 8.43 (d, 1H), 8.02-8.04 (m,1H), 7.98 (s, 1H), 7.74-7.79 (m, 2H), 7.60-7.62 (m, 2H), 7.24-7.28 (m,2H), 7.14 (d, 1H), 4.22 (s, 3H), 3.39-3.44 (m, 1H), 3.01-3.06 (m, 2H),2.82-2.92 (m, 1H), 1.99-2.18 (m, 2H), 1.80-1.82 (m, 2H). MS (EI) forC₂₄H₂₅N₆O₃F₃S: 535 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.58 (s, 1H), 8.46 (d, 1H), 7.89 (s, 1H),7.76-7.84 (m, 2H), 7.24-7.30 (m, 3H), 7.12 (d, 1H), 4.15-4.27 (m, 1H),4.13 (s, 2H), 3.39-3.43 (m, 1H), 3.01-3.07 (m, 2H), 2.91-2.93 (m, 1H),1.94-2.09 (m, 2H), 1.74-1.85 (m, 2H). MS (EI) for C₂₄H₂₅N₆O₄F₃S: 551(MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2-[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.67 (s, 1H), 8.02 (s, 1H), 7.94-8.02 (m,1H), 7.83-7.85 (m, 1H), 7.60-7.64 (m, 1H), 7.38-7.41 (m, 2H), 7.31-7.35(m, 1H), 7.21-7.23 (m, 1H), 4.29 (s, 3H), 3.47-3.53 (m, 1H), 3.11-3.16(m, 2H), 2.96-3.10 (m, 1H), 1.84-2.38 (m, 4H). MS (EI) forC₂₄H₂₅N₆O₄F₃S: 551 (MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.56 (s, 1H), 8.88 (s, 2H), 7.84 (m, 1H),7.76 (d, 1H), 8.67 (d, 2H), 7.25 (t, 1H), 7.12 (d, 1H), 4.18-4.27 (m,1H), 4.14 (s, 2H), 3.38-3.41 (m, 1H), 3.01-3.06 (m, 2H), 2.87-2.92 (m,1H), 1.80-2.06 (m, 4H). MS (EI) for C₂₄H₂₅N₆O₃F₃S: 535 (MH⁺).

3-Amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.67 (s, 1H), 7.96 (s, 1H), 7.88-7.84 (m,1H), 7.39-7.33 (m, 1H), 7.30-7.25 (m, 2H), 7.24-7.19 (m, 1H), 6.90-6.86(m, 1H), 4.38-4.27 (m, 1H), 4.26-4.19 (m, 4H), 4.16 (s, 2H), 3.54-3.46(m, 1H), 3.39-3.31 (m, 1H), 3.18-3.10 (m, 1H), 3.05-2.95 (m, 1H),2.20-2.05 (m, 2H), 1.97-1.83 (m, 2H). MS (EI) for C₂₅H₂₈N₆O₅S: 524(MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-thienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.70 (s, 1H), 8.07 (s, 1H), 7.91-7.86 (m,1H), 7.77-7.74 (m, 1H), 7.63-7.59 (m, 1H), 7.42-7.36 (m, 1H), 7.28-7.23(m, 1H), 7.14-7.10 (m, 1H), 4.37-4.25 (m, 1H), 4.23 (s, 2H), 3.54-3.45(m, 1H), 3.39-3.31 (m, 1H), 3.19-3.08 (m, 1H), 3.05-2.94 (m, 1H),2.19-2.02 (m, 2H), 1.97-1.81 (m, 2H). MS (EI) for C₂₁H₂₄N₆O₃S₂: 473(MH⁺).

3-Amino-N-[(3S)-piperidin-3-yl]-6-(3-{([(3-thienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ8.70 (s, 1H), 8.09-8.03 (m, 2H), 7.91-7.86(m, 1H), 7.60-7.55 (m, 1H), 7.41-7.33 (m, 2H), 7.27-7.21 (m, 1H),4.37-4.25 (m, 1H), 4.20 (s, 2H), 3.54-3.45 (m, 1H), 3.39-3.31 (m, 1H),3.19-3.09 (m, 1H), 3.05-2.93 (m, 1H), 2.19-2.02 (m, 2), 1.98-1.81 (m,2H). MS (EI) for C₂₁H₂₄N₆O₃S₂: 473 (MH⁺).

3-Amino-6-[3-({[(4-chlorophenyl)sulfonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.66 (s, 1H), 7.94 (s, 1H), 7.90-7.85 (m,1H), 7.81-7.75 (m, 2H), 7.50-7.45 (m, 2H), 7.39-7.33 (m, 1H), 7.25-7.20(m, 1H), 4.38-4.25 (m, 1H), 4.20 (s, 2H), 3.55-3.46 (m, 1H), 3.39-3.31(m, 1H), 3.18-3.08 (m, 1H), 3.05-2.93 (m, 1H), 2.20-2.01 (m, 2H),1.98-1.81 (m, 2H). MS (EI) for C₂₃H₂₅N₆O₃SCl: 501 (MH⁺).

N-[(2,4-Dichlorophenyl)methyl]-N′-[(1S)-2,3-dihydro-1H-inden-1-yl]benzene-1,3-dicarboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (t, J=6.0 Hz, 1H), 8.93 (d, J=8.4 Hz,1H), 8.43 (m, 1H), 8.05 (m, 2H), 7.64 (m, 1H), 7.59 (m, 1H), 7.42 (m,2H), 7.25 (m, 4H), 5.59 (m, 1H), 4.53 (m, 2H), 3.00 (m, 1H), 2.86 (m,1H), 2.47 (m, 1H), 2.01 (m, 1H). MS (EI) for C₂₄H₂₀Cl₂N₂O₂: 439 (MH⁺).

Example 643-Amino-6-{3-[({[3-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide

To a solution of3-[5-amino-6-({(3S)-1-(tert-butoxycarbonyl)piperidine-3-yl]amino}carbonyl)pyrazin-2-yl]benzoicacid (80 mg, 0.18 mmol) in dry dichloromethane (1.0 mL) were added1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC, 48 mg,0.25 mmol) and 1-hydroxybenzotriazole (HOBT, 34 mg, 0.25 mmol). Thereaction mixture was stirred for 10-15 min at room temperature. Asolution of 3-fluoro-4-(triflouromethyl)benzylamine (52 mg, 0.27 mmol)in dichloromethane (1 mL) was added and stirring continued for 2-3 h.Reaction was diluted with ethyl acetate (150 mL), washed with saturatedaqueous sodium bicarbonate (40 mL) and saturated aqueous sodium chloride(50 mL). Dried over anhydrous magnesium sulfate, filtered, concentrated,and purification on silica (7:3 hexanes/ethyl acetate) afforded theamide product. MS (EI) for C₂₈H₂₈N₆O₂F₄: 517 [(M-boc)H⁺].

To a solution of the above amide in methanol (2 mL) was added 4.0 Nhydrochloric acid (1,4-dioxane solution, 1 mL) and the reaction stirreduntil the deprotection (removal of Boc-protecting group) was completedas monitored by thin layer chromatography. The excess reagent andsolvent was removed at reduced pressure to give a solid product whichwas washed further with ethyl acetate (50 mL) to afford the hydrochloricacid salt of3-amino-6-{3-[({[3-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide(16 mg, 15% yield) as yellow solid. ¹H NMR (400 MHz, d₆-DMSO): 9.90 (s,1H), 9.25 (br s, 1H), 9.02 (m, 3H), 8.80 (s, 1H), 8.54 (d, 1H), 7.90 (d,1H), 7.60 (m, 4H), 4.60 (br s, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.70 (m,1H), 1.92 (m, 4H); MS (EI) for C₂₅H₂₄N₆O₂F₄: 517 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.80 (t, 1H), 9.20 (br s, 1H), 8.93 (m, 3H),8.70 (s, 1H), 8.58 (d, 1H), 7.90 (d, 1H), 7.60 (m, 3H), 7.40 (d, 1H),4.50 (d, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.80 (m, 1H), 1.90 (m, 4H); MS(EI) for C₂₄H₂₄N₆O₂Cl₂: 499, 501 (MH⁺).

3-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.45 (t, 1H), 9.20 (br s, 1H), 9.01 (m, 3H),8.70 (s, 1H), 8.35 (d, 1H), 7.90 (d, 1H), 7.30 (s, 1H), 7.20 (s, 2H),4.50 (m, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.70 (m, 1H), 2.38 (s, 3H),1.90 (m, 4H); MS (EI) for C₂₅H₂₇N₆O₂Cl: 479, 480 (MH⁺).

3-amino-6-{3-[({[2-chloro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.85 (t, 1H), 9.25 (br s, 1H), 9.02 (m, 3H),8.80 (s, 1H), 8.40 (d, 1H), 7.90 (d, 1H), 7.70 (m, 3H), 7.60 (t, 1H),4.64 (br s, 2H), 4.30 (m, 1H), 3.25 (m, 3H), 2.70 (m, 1H), 1.92 (m, 4H);MS (EI) for C₂₅H₂₄N₆O₂F₃Cl: 533, 534 (MH⁺).

3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.30 (br s, 1H), 9.00 (br s, 1H), 9.01 (t,1H), 8.95 (s, 1H), 8.80 (d, 1H), 8.73 (s, 1H), 8.30 (d, 1H), 7.85 (d,1H), 7.60 (t, 1H), 7.40 (m. 2H), 7.30 (t, 1H), 4.60 (s, 2H), 4.45 (m,1H), 3.30 (m, 1H), 3.12 (m, 1H), 2.70 (m, 1H), 1.92 (m, 4H); MS (EI) forC₂₄H₂₄N₆O₂FCl: 483 (MH⁺).

3-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.80 (t, 1H), 9.30 (br s, 1H), 9.02 (br s,1H), 8.92 (m, 2H), 8.70 (s, 1H), 8.30 (d, 1H), 7.90 (d, 1H), 7.60 (t,1H), 7.50 (m, 2H), 7.20 (t. 1H), 4.60 (br s, 2H), 4.30 (m, 1H), 3.20 (m,3H), 2.90 (m, 1H), 1.92 (m, 4H); MS (EI) for C₂₄H₂₄N₆O₂FCl: 483 (MH⁺).

3-amino-6-{3-[({[2-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.65 (t, 1H), 9.20 (br s, 1H), 9.00 (br s,1H), 8.90 (m, 2H), 8.70 (s, 1H), 8.30 (d, 1H), 7.90 (d, 1H), 7.80 (m,1H), 7.78 (m, 1H), 7.58 (t. 1H), 7.45 (t, 1H), 4.60 (br s, 2H), 4.32 (m,1H), 3.20 (m, 3H), 2.70 (m, 1H), 1.92 (m, 4H); MS (EI) for C₂₅H₂₄N₆O₂F₄:517 (MH⁺).

Example 653-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide

To a solution of tert-butyl(3S)-3-[({3-amino-6-[3-(methoxycarbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate(100 mg, 0.22 mmol) in tetrahydrofuran/water (4:1, 1.5 mL) was added 0.5N aqueous lithium hydroxide (0.5 mL, 0.55 mmol) and the reaction wasstirred at room temperature overnight. Reaction was diluted withdichloromethane (4 mL) and treated with 0.5 N aqueous hydrochloric acid(0.5 mL). The aqueous layer was discarded. The crude acid indichloromethane solution was treated with1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 63 mg,0.33 mmol) and 1-hydroxybenzotriazole (HOBT, 45 mg, 0.33 mmol). Thereaction was stirred for 10-15 min and then a solution of5-chloro-1,6-difluorobenzylamine (46 mg, 0.26 mmol) in dichloromethane(0.5 mL) was added. The reaction was stirred for 2-3 h and diluted withethyl acetate (150 mL). The organic layer was washed with saturatedaqueous sodium bicarbonate (40 mL), saturated aqueous sodium chloride(50 mL), and dried over anhydrous magnesium sulfate. Filtration,concentration, and purification on silica (3:7 hexanes/ethyl acetate)afforded the boc-protected intermediate. MS (EI) for C₂₄H₂₃N₆O₂F₂Cl:501, 503 [(M-boc)H⁺].

To a solution of the above intermediate in methanol (2 mL) was added 4.0N hydrochloric acid (1,4-dioxane solution, 1 mL) and the reactionstirred until the deprotection was completed as monitored by thin layerchromatography. The excess reagent and solvent was removed at reducedpressure to give a solid product which was washed further with ethylacetate (50 mL) to afford the hydrochloric acid salt of3-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide(76 mg, 69% yield) as yellow solid ¹H NMR (400 MHz, d₆-DMSO): 9.26 (m,2H), 9.10 (m, 1H), 8.90 (s, 1H), 8.80 (d, 1H), 8.60 (s, 1H), 8.35 (d,1H), 7.60 (m, 2H), 7.20 (t, 1H), 7.20 (t, 1H), 4.60 (br s, 2H), 4.30 (m,1H), 3.20 (m, 3H), 3.10 (m, 1H), 2.80 (m, 1H), 1.90 (m, 2H), 1.80 (m,2H); MS (EI) for C₂₄H₂₃N₆O₂F₂Cl: 501, 503 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-6-{3-[({[2-fluoro-4-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.70 (t, 1H), 9.30 (br s, 1H), 9.10 (br s,1H), 9.01 (m, 2H), 8.80 (s, 1H), 8.36 (d, 1H), 7.90 (d, 1H), 7.60 (m,6H), 4.60 (br s, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.78 (m, 1H), 1.90 (m,4H); MS (EI) for C₂₅H₂₄N₆O₂F₄: 517 (MH⁺).

3-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.54 (m, 1H), 9.25 (br s, 1H), 9.02 (m, 3H),8.74 (s, 1H), 8.34 (d, 1H), 7.90 (d, 1H), 7.50 (m, 4H), 7.20 (t, 1H),4.58 (br s, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.75 (m, 1H), 1.92 (m, 4H);MS (EI) for C₂₄H₂₄N₆O₂F₂Cl: 483, 485 (MH⁺).

3-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): 9.80 (t, 1H), 9.20 (br s, 1H), 9.01 (m, 3H),8.74 (s, 1H), 8.30 (d, 1H), 7.90 (d, 1H), 7.60 (m, 2H), 7.40 (m, 2H),4.60 (d, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.74 (m, 1H), 1.92 (m, 4H); MS(EI) for C₂₄H₂₄N₆O₂Cl₂: 499, 500 (MH⁺).

3-amino-N-[(3S)-piperidin-3-yl)-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): 9.23 (m, 2H), 9.02 (br s, 1H), 8.90 (s, 1H),8.80 (d, 1H), 8.32 (d, 1H), 7.60 (t, 1H), 7.50 (m, 1H), 7.20 (m, 1H),4.60 (d, 2H), 4.34 (m, 1H), 3.30 (m, 2H), 3.10 (m, 1H), 2.80 (m, 1H),1.90 (m, 2H), 1.80 (m, 2H); MS (EI) for C₂₄H₂₃N₆O₂F₃: 485 (MH⁺).

3-amino-6-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.80 (m, 2H), 9.30 (br s, 1H), 9.04 (m, 3H),8.74 (s, 1H), 8.30 (d, 1H), 7.90 (m, 2H), 7.70 (s, 2H), 7.60 (t, 1H),4.60 (d, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.80 (m, 1H), 1.90 (m, 4H); MS(EI) for C₂₅H₂₄N₆O₂F₃Cl: 533, 534 (MH⁺).

3-amino-6-[3-({[(3-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.82 (m, 1H), 9.30 (br s, 1H), 9.02 (m, 3H),8.78 (s, 1H), 8.50 (d, 1H), 7.90 (m, 1H), 7.70 (s, 2H), 7.60 (m, 2H),7.40 (m, 2H), 4.50 (d, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.80 (m, 1H),1.92 (m, 4H); MS (EI) for C₂₄H₂₄N₆O₂FCl: 483, 485 (MH⁺).

3-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.20 (br s, 1H), 9.10 (m, 1H), 8.95 (m, 2H),8.80 (d, 1H), 8.74 (s, 1H), 8.30 (d, 1H), 7.84 (d, 1H), 7.60 (t, 1H),7.40 (m, 1H), 7.10 (m, 2H), 4.60 (d, 2H), 4.30 (m, 1H), 3.30 (m, 2H),3.06 (m, 1H), 2.78 (m, 1H), 1.90 (m, 2H), 1.74 (m, 2H); MS (EI) forC₂₄H₂₄N₆O₂F: 467 (MH⁺).

3-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.80 (m, 1H), 9.20 (br s, 1H), 8.99 (m, 3H),8.70 (s, 1H), 8.30 (d, 1H), 7.90 (d, 1H), 7.60 (t, 1H), 7.40 (m, 2H),7.20 (br s, 1H), 4.60 (br s, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.80 (m,1H), 1.92 (m, 4H); MS (EI) for C₂₄H₂₄N₆O₂F₂: 467 (MH⁺).

3-amino-6-[3-({[(6-chloro-2-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.20 (br s, 1H), 8.90 (m, 3H), 8.75 (d, 1H),8.50 (s, 1H), 8.30 (d, 1H), 7.86 (d, 1H), 7.60 (t, 1H), 7.40 (m, 2H),7.20 (t, 1H), 4.60 (br s, 2H), 4.30 (m, 1H), 3.30 (m, 2H), 3.02 (m, 1H),2.80 (m, 1H), 2.30 (s, 3H), 1.92 (m, 2H), 1.80 (m, 2H); MS (EI) forC₂₅H₂₆N₆O₂F₁Cl: 497,499 (MH⁺).

3-amino-6-[3-({[(2-chloro-6-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.30 (m, 1H), 9.10 (m, 1H), 8.90 (m, 2H),8.80 (d, 1H), 8.70 (s, 1H), 8.30 (d, 1H), 7.84 (d, 1H), 7.60 (t, 1H),7.30 (m, 2H), 4.60 (br s, 2H), 4.30 (m, 1H), 3.30 (m, 2H), 3.02 (m, 1H),2.80 (m, 1H), 2.30 (s, 3H), 1.92 (m, 2H), 1.74 (m, 2H); MS (EI) forC₂₅H₂₆N₆O₂F₁Cl: 497, 499 (MH⁺).

3-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.40 (m, 1H), 9.20 (br s, 1H), 8.94 (s, 1H),8.85 (d, 1H), 8.72 (s, 1H), 8.57 (d, 1H), 7.90 (d, 1H), 7.60 (t, 1H),7.24 (m, 1H), 7.15 (m, 1H), 7.02 (m, 1H), 4.50 (br s, 2H), 4.30 (m, 1H),3.20 (m, 3H), 2.80 (m, 1H), 2.30 (s, 3H), 1.90 (m, 4H); MS (EI) forC₂₅H₂₇N₆O₂F: 463 (MH⁺).

3-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.50 (m, 1H), 9.10 (br s, 1H), 8.94 (s, 1H),8.90 (d, 1H), 8.70 (s, 1H), 8.40 (d, 1H), 7.90 (d, 1H), 7.60 (t, 1H),7.40 (s, 1H), 7.25 (m, 2H), 4.50 (br s, 2H), 4.30 (m, 1H), 3.20 (m, 3H),2.80 (m, 1H), 2.30 (s, 3H), 1.90 (m, 4H); MS (EI) for C₂₅H₂₇N₆O₂FCl:479, 481 (MH⁺).

3-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.30 (br s, 1H), 9.10 (br s, 1H), 8.90 (s,1H), 8.84 (d, 1H), 8.63 (s, 1H), 8.30 (m, 2H), 7.84 (d, 1H), 7.60 (t,1H), 7.30 (t, 1H), 6.70 (d, 2H), 4.45 (br s, 2H), 4.20 (m, 1H), 3.80 (s,6H), 3.20 (m, 2H), 2.90 (m, 1H), 2.70 (s, 1H), 1.80 (m, 4H); MS (EI) forC₂₆H₃₀N₆O₄: 491 (MH⁺).

3-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.80 (m, 1H), 9.30 (br s, 1H), 9.01 (m, 3H),8.85 (s, 1H), 8.34 (d, 1H), 7.90 (d, 1H), 7.70 (d, 1H), 7.60 (t, 1H),7.40 (m, 2H), 4.50 (br s, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.80 (m, 1H),1.90 (m, 4H); MS (EI) for C₂₄H₂₄N₆O₂FBr: 427, 429 (MH⁺).

3-amino-6-[3-([{(3-bromo-5-fluorophenyl)methyl]amino)carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.50 (m, 1H), 9.20 (br s, 1H), 8.98 (m, 2H),8.70 (s, 1H), 8.36 (d, 1H), 7.90 (d, 1H), 7.60 (m, 3H), 7.20 (t, 1H),4.50 (br s, 2H), 4.30 (m, 1H), 3.20 (m, 3H), 2.70 (m, 1H), 1.90 (m, 4H);MS (EI) for C₂₄H₂₄N₆O₂FBr: 527, 529 (MH⁺).

3-amino-6-{3-[({[(3-methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): 9.50 (t, 1H), 9.30 (br s, 1H), 8.90 (m, 2H),8.70 (s, 1H), 8.35 (d, 1H), 7.90 (d, 1H), 7.60 (m, 3H), 7.22 (t, 1H),6.93 (br s, 1H), 6.80 (d, 1H), 4.50 (br s, 2H), 4.30 (m, 1H), 3.73 (s,3H), 3.20 (m, 3H), 2.70 (m, 1H), 1.90 (m, 4H); MS (EI) for C₂₅H₂₈N₆O₃:461 (MH⁺).

3-amino-6-{3-[({[3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.30 (s, 1H), 9.20 (br s, 1H), 8.95 (m, 2H),8.86 (d, 1H), 8.60 (s, 1H), 8.30 (d, 1H), 7.86 (d, 1H), 7.58 (t, 1H),7.02 (s, 1H), 6.87 (br s, 2H), 4.50 (d, 2H), 4.30 (m, 1H), 3.74 (s, 3H),3.72 (s, 3H), 3.25 (m, 2H), 3.15 (m, 1H), 2.70 (m, 1H), 1.90 (m, 4H); MS(EI) for C₂₆H₃₀N₆O₄: 491 (MH⁺).

3-amino-6-[3-({[(2-chloro-3,6-difluorophenyl)methyl]amino)carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.31 (s, 1H), 9.09 (s, 2H), 8.93 (s, 1H),8.80 (d, 1H), 8.56 (s, 1H), 8.33 (d, 1H), 7.86 (d, 1H), 7.57 (t, 1H),7.48 (m, 1H), 7.35 (m, 1H), 4.65 (m, 2H), 4.37 (m, 1H), 3.29 (m, 2H),3.05 (m, 1H), 2.74 (m,1H), 1.99-1.72 (m, 4H); MS (EI) forC₂₄H₂₃N₆O₂F₂Cl: 501.04 (MH⁺).

3-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.61 (t, 1H), 9.15 (m, 1H), 8.97 (s, 1H),8.96 (s, 1H), 8.94 (s, 1H), 8.77 (s, 1H), 8.36 (d, 1H), 7.94 (d, 1H),7.61 (t, 1H), 7.53 (d, 1H), 7.44-7.39 (m, 2H), 4.57 (m, 2H), 4.29 (m,1H), 3.28-3.16 (m, 3H), 2.76 (m, 1H), 1.91-1.72 (m, 4H); MS (EI) forC₂₄H₂₄N₆O₂Cl₂: 500.98 (MH⁺).

3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,4-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.56 (s, 1H), 9.18 (s, 1H), 9.00 (s, 1H),8.96 (s, 1H), 8.92 (d, 1H), 8.70 (s, 1H), 8.34 (d, 1H), 7.89 (d, 1H),7.59 (t, 1H), 7.32 (m, 2H), 4.55 (d, 2H), 4.28 (m, 1H), 3.29-3.15 (m,3H), 2.76 (m, 1H), 1.91-1.73 (m, 4H); MS (EI) for C₂₄H₂₃N₆O₂F₃: 485.06(MH⁺).

3-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.60 (s, 1H), 9.28 (s, 1H), 9.06 (s, 1H),8.96 (s, 1H), 8.94 (s, 1H), 8.73 (s, 1H), 8.34 (d, 1H), 7.90 (d, 1H),7.59 (t, 1H), 7.37-7.16 (m, 3H), 4.60 (m, 2H), 4.30 (m, 1H), 3.27-3.15(m, 3H), 2.77 (m, 1H), 1.92-1.73 (m, 4H); MS (EI) for C₂₄H₂₄N₆O₂F₂:467.06 (MH⁺).

3-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.55 (s, 1H), 9.28 (s, 1H), 9.08 (s, 1H),8.96 (m, 2H), 8.72 (s, 1H), 8.33 (d, 1H), 7.91 (d, 1H), 7.59 (t, 1H),7.24 (t, 1H), 7.15-7.10 (m, 2H), 4.50 (m, 2H), 4.30 (m, 1H), 3.29-3.13(m, 3H), 2.76 (m, 1H), 2.20 (s, 3H), 1.94-1.71 (m, 4H); MS (EI) forC₂₅H₂₇N₆O₂F: 463.12 (MH⁺).

3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.72 (m, 1H), 9.23 (s, 1H), 9.00 (m, 2H),8.96 (s, 1H), 8.78 (s, 1H), 8.33 (d, 1H), 7.91 (d, 1H), 7.59 (t, 1H),7.36 (m, 2H), 4.49 (m, 2H), 4.30 (m, 1H), 3.28-3.17 (m, 3H), 2.76 (m,1H), 1.94-1.70 (m, 4H); MS (EI) for C₂₄H₂₃N₆O₂F₃: 485.28 (MH⁺).

3-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.51 (m, 1H), 9.29 (s, 1H), 9.08 (s, 1H),8.94 (m, 2H), 8.70 (s, 1H), 8.33 (d, 1H), 7.91 (d, 1H), 7.58 (t, 1H),7.25 (m, 2H), 7.09 (t, 1H), 4.46 (m, 2H), 4.29 (m, 1H), 3.30-3.13 (m,3H), 2.76 (m, 1H), 2.22 (s, 1H), 1.94-1.70 (m, 4H); MS (EI) forC₂₅H₂₇N₆O₂F: 463.31 (MH⁺).

3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.67 (s, 2H), 9.21 (s, 1H), 8.99 (s, 2H),8.75 (m, 1H), 8.34 (d, 1H), 7.90 (d, 1H), 7.59 (t, 1H), 7.46 (m, 1H),7.16 (m, 1H), 4.58 (m, 2H), 4.29 (m, 1H), 3.22 (m, 3H), 2.75 (m, 1H),1.95-1.68 (m, 4H); MS (EI) for C₂₄H₂₃N₆O₂F₃: 485.27 (MH⁺).

3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.63 (s, 1H), 9.36 (s, 1H), 9.14 (s, 1H),8.98 (m, 2H), 8.76 (s, 1H), 8.48 (d, 1H), 8.34 (d, 1H), 7.93 (d, 1H),7.81 (d, 2H), 7.73 (d, 1H), 7.59 (t,1H), 7.51 (d, 2H), 6.54 (m, 1H),4.56 (m, 2H), 4.31 (m, 1H), 3.32-3.12 (m, 3H), 2.75 (m, 1H), 1.94-1.69(m, 4H); MS (EI) for C₂₇H₂₈N₈O₂: 497.06 (MH⁺).

3-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.60 (t, 1H), 9.31 (s, 1H), 9.08 (s, 1H),8.94 (m, 2H), 8.74 (s, 1H), 8.34 (d, 1H), 7.93 (d, 1H), 7.68-7.34 (m,10H), 4.60 (m, 2H), 4.29 (m, 1H), 3.30-3.11 (m, 3H), 2.74 (m, 1H),1.941.67 (m, 4H); MS (EI) for C₃₀H₃₀N₆O₂: 507.07 (MH⁺).

3-amino-6-[3-({[(2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.33 (t, 2H), 9.11 (m, 1H), 8.96 (s, 1H),8.92 (d, 1H), 8.71 (s, 1H), 8.34 (d, 1H), 7.92 (d, 1H), 7.59 (t, 1H),7.32 (m, 1H), 7.17 (m, 3H), 4.50 (m, 2H), 4.29 (m, 1H), 3.30-3.06 (m,3H), 2.74 (m, 1H), 2.36 (s, 1H), 1.94-1.66 (m, 4H); MS (EI) forC₂₅H₂₈N₆O₂: 445.08 (MH⁺).

3-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.34 (s, 1H), 9.28 (m, 1H), 9.13 (s,1H), 8.96(s, 1H), 8.91 (d, 1H), 8.69 (s, 1H), 8.34 (d, 1H), 7.92 (d, 1H), 7.59(t, 1H), 7.11 (s, 1H), 7.06 (d, 1H), 6.97 (d,1H), 4.46 (m, 2H), 4.29 (m,1H), 3.32-3.02 (m, 3H), 2.74 (m, 1H), 2.31 (s,3H), 2.24 (s,3H),1.97-1.67 (m, 4H); MS (EI) for C₂₆H₃₀N₆O₂: 459.09 (MH⁺).

3-amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.39 (s, 1H), 9.28 (s, 1H), 9.06 (s,1H), 8.95(s, 1H), 8.91 (d, 1H), 8.68 (s, 1H), 8.34 (d, 1H), 7.92 (d, 1H), 7.59(t, 1H), 6.96 (s, 2H), 6.87 (s,1H), 4.44 (m, 2H), 4.28 (m, 1H),3.31-3.08 (m, 3H), 2.74 (m, 1H), 2.31 (s, 6H), 1.95-1.66 (m, 4H); MS(EI) for C₂₆H₃₀N₆O₂: 459.09 (MH⁺).

3-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.29 (s, 1H), 9.23 (t, 1H), 9.08 (m,1H), 8.95(s, 1H), 8.91 (d, 1H), 8.66 (s, 1H), 8.33 (d, 1H), 7.91 (d, 1H), 7.58(t, 1H), 7.20 (d,1H), 6.99 (s, 1H), 6.96 (d,1H), 4.45 (m, 2H), 4.28 (m,1H), 3.27-3.05 (m, 3H), 2.74 (m, 1H), 2.32 (s, 3H), 2.24 (s, 3H),1.96-1.67 (m, 4H); MS (EI) for C₂₆H₃₀N₆O₂: 459.09 (MH³⁰).

3-amino-6-{3-[({[phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.48 (t, 1H), 9.26 (m, 1H), 9.05 (m, 1H),8.96 (s, 1H), 8.92 (d, 1H), 8.70 (s, 1H), 8.34 (d, 1H), 7.91 (d, 1H),7.59 (t, 1H), 7.40-7.31 (m, 4H), 7.28-7.22 (m, 1H), 4.53 (m, 2H), 4.29(m, 1H), 3.32-3.07 (m, 3H), 2.75 (m, 1H), 1.95-1.67 (m, 4H); MS (EI) forC₂₄H₂₆N₆O₂: 431.09 (MH⁺).

3-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₆): 9.46 (t, 1H), 9.31 (m, 1H), 9.10 (m, 1H),8.96 (s, 1H), 8.94 (d, 1H), 8.70 (s, 1H), 8.34 (d, 1H), 7.91 (d, 1H),7.59 (t, 1H), 6.54 (d, 2H), 6.39 (t, 1H), 4.45 (m, 2H), 4.29 (m, 1H),3.72 (s, 6H), 3.34-3.10 (m, 3H), 2.75 (m,1H), 1.96-1.66 (m, 4H); MS (EI)for C₂₆H₃₀N₆O₄: 491.06 (MH⁺).

Example 663-amino-6-(3-{[(2-methylphenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide

To a solution of 2-methylphenylacetic acid (45 mg, 0.30 mmol) in drydichloromethane (1.0 mL) were added1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 72 mg,0.38 mmol) and 1-hydroxybenzotriazole (HOBT, 51 mg, 0.38 mmol). Thereaction mixture was stirred for 10-15 min at room temperature. Asolution of tert-butyl(3S)-3-({[3-amino-6-(3-aminophenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate(80 mg, 0.20 mmol) in dichloromethane (1 mL) was added and stirringcontinued for 2-3 h. Reaction was diluted with ethyl acetate (150 mL),washed with saturated aqueous sodium bicarbonate (40 mL) and saturatedaqueous sodium chloride (50 mL). Dried over anhydrous magnesium sulfate,filtered, concentrated, and purification on silica (hexanes/ethylacetate, 3:7) afforded the protected intermediate. MS (EI) forC₂₅H₂₈N₆O₂: 445 [(M-boc)H⁺].

To a solution of the above intermediate in methanol (2 mL) was added 4.0N hydrochloric acid (1,4-dioxane solution, 1 mL) and the reactionstirred until the deprotection was completed as monitored by thin layerchromatography. The excess reagent and solvent was removed at reducedpressure to give a solid product which was washed further with ethylacetate (50 mL) to afford the hydrochloric acid salt of3-amino-6-(3-{[(2-methylphenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide(56 mg, 63% yield) as yellow solid. ¹NMR (400 MHz, d₆-DMSO): 10.72 (s,1H), 9.20 (br s, 1H), 9.04 (br s, 1H), 8.80 (s, 1H), 8.70 (d, 1H), 8.45(s, 1H), 7.80 (d, 1H), 7.40 (m, 2H), 7.18 (m, 3H), 4.32 (m, 1H), 3.80(s, 2H), 3.25 (m, 3H), 2.80 (m, 1H), 2.3 (s, 3H), 1.80 (m, 4H); MS (EI)for C₂₅H₂₈N₆O₂: 445 (MH+).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents as described above, the following compounds ofthe invention were prepared:

3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[3-(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide:¹NMR (400 MH, d₆-DMSO): 10.82 (s, 1H), 9.10 (br s, 1H), 8.92 (br s, 1H),8.90 (s, 1H), 8.85 (d, 1H), 8.40 (s, 1H), 7.72 (m, 6H), 7.40 (t, 1H),4.40 (m, 1H), 3.84 (s, 2H), 3.25 (m, 3H), 2.80 (m, 1H), 1.84 (m, 4H); MS(EI) for C₂₅H₂₅N₆O₂F₃: 499 (MH⁺).

3-amino-6-[3-({[4-(methyloxy)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹NMR (400 MHz, d₆-DMSO): 10.60 (s, 1H), 9.10 (br s, 1H), 9.01 (br s,1H), 8.78 (s, 1H), 8.68 (d, 1H), 8.40 (s, 1H), 7.80 (t, 1H), 7.40 (t,1H), 7.30 (d, 2H), 6.85 (d, 2H), 4.45 (m, 1H), 3.72 (s, 3H), 3.60 (s,2H), 3.25 (m, 3H), 2.80 (m, 1H), 1.90 (m, 4H); MS (EI) for C₂₅H₂₈N₆O₃:461 (MH⁺).

3-amino-6-(3-{[(6-methylpyridin-3-yl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹NMR (400 MHz, d₆-DMSO): 11.40 (s, 1H), 9.60 (s, 1H), 9.50 (br s, 1H),9.10 (m, 2H), 8.90 (m, 3H), 8.15 (d, 1H), 8.00 (d, 1H), 7.90 (d, 1H),7.50 (t, 2H), 4.40 (m, 1H), 3.30 (m, 3H), 2.90 (m, 4H), 1.80 (m, 4H); MS(EI) for C₂₃H₂₅N₇O₂: 432 (MH⁺).

3-amino-6-(3-{[(3-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹NMR (400 MHz, d₆-DMSO): 10.80 (s, 1H), 9.10 (br s, 1H), 8.95 (br s,1H), 8.80 (s, 1H), 8.70 (d, 1H), 8.40 (s, 1H), 7.80 (m, 2H), 7.40 (m,2H), 7.30 (m, 2H), 7.10 (t, 1H), 4.30 (m, 1H), 3.75 (s, 2H), 3.22 (m,3H), 2.80 (m, 1H), 1.90 (m, 4H); MS (EI) for C₂₄H₂₅N₆O₂F: 449 (MH⁺).

3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3-ylacetyl)amino]phenyl}pyrazine-2-carboxamide:¹NMR (400 MHz, d₆-DMSO): 11.15 (s, 1H), 9.28 (br s, 1H), 9.02 (m, 2H),8.90 (d, 1H), 8.78 (s, 1H), 8.65 (d, 1H), 8.60 (d, 1H), 8.50 (s, 1H),8.02 (m, 1H), 7.80 (m, 2H), 7.40 (t, 1H), 4.30 (m, 1H), 3.30 (m, 3H),2.80 (m, 1H), 1.92 (m, 4H); MS (EI) for C₂₃H₂₅N₇O₂: 432 (MH⁺).

3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3-ylcarbonyl)amino]phenyl}pyrazine-2-carboxamide:¹NMR (400 MHz, d₆-DMSO): 11.30 (s, 1H), 9.80 (s, 1H), 9.30 (br s, 1H),9.02 (m, 3H), 8.80 (m, 3H), 8.10 (d, 1H), 8.01 (m, 1H), 7.90 (d, 1H),7.45 (t, 1H), 4.30 (m, 1H), 3.35 (m, 3H), 2.78 (m, 1H), 1.90 (m, 4H); MS(EI) for C₂₂H₂₃N₇O₂: 418 (MH⁺).

3-amino-6-(3-{[(2,5-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹NMR (400 MH, d₆-DMSO): 10.75 (s, 1H), 9.10 (br s, 1H), 9.01 (br s, 1H),8.80 (s, 1H), 8.70 (d, 1H), 8.60 (s, 1H), 7.80 (m, 2H), 7.40 (t, 1H),7.32 (m, 3H), 4.30 (m, 1H), 3.80 (s, 2H), 3.20 (m, 3H), 2.78 (m, 1H),1.90 (m, 4H); MS (EI) for C₂₄H₂₄N₆O₂F₂: 467 (MH⁺).

3-amino-6-(3-{[(4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹NMR (400 MHz, d₆-DMSO): 10.72 (s, 1H), 9.18 (br s, 1H), 9.02 (br s,1H), 8.80 (s, 1H), 8.70 (d, 1H), 7.80 (m, 2H), 7.40 (m, 3H), 7.20 (m,2H), 4.24 (m, 1H), 3.73 (s, 2H), 3.30 (m, 3H), 2.80 (m, 1H), 1.92 (m,4H); MS (EI) for C₂₄H₂₅N₆O₂F: 449 (MH+).

Example 67

Scheme 25 depicts three exemplary compounds, (ciii), (civ), and (cv),the latter two according to formula I, which are useful as intermediatesto synthesize other compounds of the invention, particularly assembling—W—X—Y. The general methods described above are used in variouscombinations to make compounds, (ciii), (civ), and (cv). Exemplarysyntheses of such compounds follows

1,1-dimethylethyl(3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate

3-amino-6-bromopyrazine-2-carboxylic acid (3.63 g, 16.65 mmol), HATU(9.49 g, 25.0 mg) and DIEA (4.35 mL, 25.0 mmol) was added to a solutionof (s)-3-amino-piperidine-1-carboxylic acid tert-butyl ester (4.00 g,19.97 mmol, commercially available from Astatech or Arch Corporation).It was stirred at room temperature overnight. The reaction mixture waspoured into water (200 mL), and extracted with ethyl acetate (2×150 mL)then dried over anhydrous sodium sulfate and filteration, concentrationand purified by column chromatography to give 1,1-dimethylethyl(3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate5.00 g (75.0% yield): MS (EI) for C₁₅H₂₂BrN₅O₃: 401.12 (MH⁺).

1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2yl}carbonyl)amino]piperidine-1-carboxylate

1,1-dimethylethyl(3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate(765.0 mg, 1.91 mmol) was dissolved in DMF followed by addition of3-hydroxymethyl phenylboronic acid (349.0 mg, 2.23 mmol), K₂CO₃ (660.0mg, 4.77 mmol) and Pd(PPh₃)₄ (10 mol %, 220 mg). This mixture wasstirred at 90° C. under nitrogen for 12 hours. The reaction mixture waspoured into water (150 mL), and extracted with ethyl acetate (3×50 mL).The organic layers were washed with brine (50 mL) then dried overanhydrous sodium sulfate. Filteration, concentration and columnchromatography on silica (50% ethylacetate/hexanes) gave a solid whichwas dried to affored 765.0 mg (92% yield) of 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2yl}carbonyl)amino]piperidine-1-carboxylate:MS (EI) for C₂₂H₂₉N₅O₄: 428.23 (MH⁺).

1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate

1,1-Dimethylethyl(3S)-3-[({3-amino-6-[3-hydroxymethyl)phenyl]pyrazin-2yl}carbonyl)amino]piperidine-1-carboxylate(965.0 mg, 2.26 mmol) was dissolved in THF (20 mL) followed by theaddition of diphenylphosphoryl azide (0.68 mL, 3.16 mmol) and DBU (0.50mL, 3.16 mmol). It was stirred at room temperature overnight. Thereaction mixture was poured into water (100 mL), and extracted withethyl acetate (2×50 mL) then dried over anhydrous sodium sulfate andfilteration, concentration and purified by column chromatography(20%→50% Ethylacetae/hexanes) to give the corresponding azide, 588.0 mg(57.6% yield) and then it was dissolved in the mixture of THF (20 mL)and H₂O (2.0 mL) followed by the addition of triphenylphosphine (1.02 g,3.88 mmol) and it was stirred at room temperature overnight. Thereaction mixture was poured into water (100 mL), and extracted withethyl acetate (2×50 mL) then dried over anhydrous sodium sulfate andfilteration, concentration and purified by column chromatography (100%Ethylacetate→100% MeON) to give 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(amino-methyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate,435.0 mg (78.8% yield): MS (EI) for C₂₂H₃₀N₆O₃: 427.24 (MH⁺).

Example 683-Amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide

1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(amino-methyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate(150.0 mg, 0.35 mmol) and 4-fluorobenzoic acid (50.0 mg, 0.36 mmol) wasdissolved in DMF (5 mL) followed by the addition of HOBT (95.5 mg, 0.70mmol) and EDCI (135.4 mg, 0.70 mmol). It was stirred at room temperatureovernight. The reaction mixture was poured into water (20 mL), andextracted with ethyl acetate (2×30 mL) then dried over anhydrous sodiumsulfate and filteration, concentration and purified by columnchromatography (50% Ethylacetae/hexanes) and subsequently it was treatedwith 4.0 M HCl in dioxane (20 mL) to give compound3-Amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:70.0 mg (46.6% yield). ¹H NMR (400 MHz, d4-MeOH): δ 8.62 (s, 1H), 8.16(s, 1H), 7.98 (m, 3H), 7.48 (m, 2H), 7.20 (m, 3H), 4.67(s, 2H), 4.38 (m,1H), 3.45 (m, 1H), 3.38 (m, 1H), 3.18 (m, 1H), 3.00 (m, 1H), 2.18 (m,2H), 1.80 (m, 2H); MS (EI) for C₂₄H₂₅N₆O₂F: 449.32 (MH⁺).

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents {respective corresponding amines, etc.}, thefollowing compounds of the invention were prepared.

3-amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.50 (m, 2H), 9.30 (br,1H), 8.78(d, 1H),8.20 (s, 1H), 8.00 (m, 3H), 7.60 (m, 2H), 7.40 (m, 2H), 5.00 (br, 2H),4.67(d, 2H), 4.38 (m, 1H), 3.20 (m, 3H), 2.80 (m, 1H), 1.80 (m, 4H); MS(EI) for C₂₄H₂₅N₆O₂Cl: 465.21 (MH⁺).

3-amino-6-{3-[({[5-(4-nitrophenyl)furan-2-yl]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ 8.62 (s, 1H), 8.38 (d, 2H), 8.10(d, 3H),7.98 (d, 1H), 7.50 (m, 2H), 7.30 (dd, 2H), 4.70 (s, 2H), 4.30 (br, 1H),3.70 (m, 1H), 3.50 (m, 1H), 3.38 (m, 1H), 3.17 (m, 1H), 3.00 (m, 1H),2.10 (m, 2H), 1.80 (m, 2H); MS (EI) for C₂₈H₂₈N₇O₅: 543.28 (MH⁺).

3-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d4-MeOH): δ; 8.70 (s, 1H), 8.40 (d, 2H), 8.10(m, 1H),8.00 (m, 1H), 7.40 (m, 1H), 7.30 (m, 1H), 4.80 (s, 1H), 4.40 (br, 1H),4.08 (s, 2H), 3.70 (m, 1H), 3.50 (m, 1H), 3.40 (m, 1H), 3.20 (m, 1H),3.10 (m, 1H), 2.10 (m, 2H), 1.80 (m, 2H); MS (EI) for C₂₃H₂₅N₇O₃: 448.28(MH⁺).

3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ; 9.20 (m, 1H), 9.00 (m, 1H), 8.92 (m, 1H),8.70 (d, 1H), 8.00 (m, 2H), 7.40 (m, 1H), 7.28 (m, 3H), 7.00 (m, 2H),4.60 (s, 1H), 4.40 (d, 2H), 4.25 (m, 1H), 3.20 (m, 4H), 2.70 (m, 1H),1.80 (m, 3H); MS (EI) for C₂₆H₂₇N₆O₄F₃: 545.26 (MH⁺).

3-amino-6-[3-({[(5-methylisoxazol-3-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ; 9.40 (m, 1H), 9.20 (m, 1H), 9.00 (m, 1H),8.60 (d, 1H), 8.00 (m, 2H), 7.40 (m, 1H), 7.28 (m, 1H), 6.60 (s, 1H),4.50 (d, 2H), 4.20 (m, 1H), 3.20 (m, 4H), 2.75 (m, 1H), 2.45 (s, 3H),1.80 (m, 3H); MS (EI) for C₂₂H₂₅N₇O₃: 436.25 (MH⁺).

3-amino-6-(3-{[(isoxazol-5-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ; 9.70 (m, 1H), 9.20 (m, 1H), 9.00 (m, 1H),8.70 (d, 1H), 8.68 (m, 1H), 8.15 (s, 1H), 8.00 (d, 1H), 7.40 (m, 1H),7.30 (m, 1H), 7.20 (s, 1H), 4.50 (d, 2H), 4.20 (m, 1H), 3.20 (m, 4H),2.75 (m, 1H), 1.80 (m, 3H); MS (EI) for C₂₁H₂₃N₇O₃: 422.23 (MH⁺).

3-amino-6-[3-({[(4-methyl-1,2,3-thiadiazol-5-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ; 9.60 (m, 1H), 9.20 (m, 1H), 9.00 (m, 1H),8.70 (d, 2H), 8.15 (s, 1H), 8.00 (d, 1H), 7.40 (m, 2H), 4.50 (d, 2H),4.20 (m, 1H), 3.20 (m, 4H), 2.80 (s, 3H), 2.75 (m, 1H), 1.80 (m, 3H); MS(EI) for C₂₁H₂₄N₈O₂S: 453.25 (MH⁺).

3-amino-6-[3-({[(2,5-dichloro-3-thienyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 9.40 (m, 1H), 9.20 (m, 1H), 9.80 (s, 1H),8.70 (d, 1H), 8.20 (s, 1H), 8.00 (d, 1H), 7.60 (s, 1H), 7.40 (m, 2H),4.50 (d, 2H), 4.30 (m, 1H), 3.70 (m, 1H), 3.50 (m, 1H), 3.20 (m, 2H),2.80 (m, 1H), 1.80 (m, 3H); MS (EI) for C₂₂H₂₂N₆O₂SCl₂: 505.12 (MH⁺).

3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d6-DMSO): δ 10.30 (br, 1H), 9.50 (m, 1H), 9.28 (m, 1H),8.90 (m, 2H), 8.15 (m, 1H), 7.90 (m, 1H), 7.50 (m, 2H), 7.38 (m, 1H),7.20 9 m, 1H), 4.20 (m, 4H), 3.40 (m, 2H), 3.20 (m, 2H), 2.70 (m, 1H),2.00 (m, 1H), 1.80 (m, 3H); MS (EI) for C₂₄H₂₆N₆OF₂: 453.25 (MH⁺).

Example 69

Example 69 describes synthesis of azepan derivatives according toformula I. Generally, but not necessarily, the synthetic strategiesfollow those described above.

3-Amino-N-azepan-3-yl-6-(3-}[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide

To a solution of3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxylicacid (409 mg, 1.09 mmol) were added azepan-3-amine (125 mg, 1.09 mmol),EDCI (252 mg, 1.31 mmol), HOBt (178 mg, 1.31 mmol) at ambienttemperature. After being stirred for 2 h, the reaction mixture wasquenched by addition of aqueous sodium bicarbonate followed byextraction with ethyl acetate (20 mL×3). The aqueous phase was extractedonce with additional ethyl acetate. The combined organic layers werewashed with saturated aqueous sodium chloride then dried over anhydrousmagnesium sulfate. Filtration and concentration in vacuo gave a crudeoil, which was purified by preparative HPLC to yield the3-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide(22 mg, 4.2% yield): ¹H NMR (400 MHz, CD₃OD): δ 8.70 (m, 1H), 8.67 (m,1H), 8.27 (m, 1H) 7.97 (m, 1H), 7.62 (t, 1H), 7.25 (m, 4H), 5.70 (m,1H), 4.99 (m, 1H), 4.43 (m, 1H), 3.46 (m, 2H), 3.38 (m, 1H), 3.15 (m,2H), 2.94 (m, 1H), 2.61 (m, 1H), 2.17 (m, 2H), 1.95 (m, 4H), 1.62 (m,1H); MS (EI) for C₂₇H₃₀N₆O₂: 471.32 (MH⁺).

3-Amino-6-[3-({[(2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide

3-Amino-6-[3-({[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxylicacid (1.0 eq) was dissolved in DMF-THF and treated with(3S)-1-(phenylmethyl)azepan-3-amine (1.46 eq), EDCI (1.2 eq) and HOBt(1.2 eq) at ambient temperature. After being stirred overnight, thereaction mixture was quenched by addition of aqueous sodium bicarbonatefollowed by extraction with ethyl acetate (20 mL×3). The aqueous phasewas extracted once with additional ethyl acetate. The combined organiclayers were washed with saturated aqueous sodium chloride then driedover anhydrous magnesium sulfate. Filtration and concentration in vacuogave a crude oil, which was purified by preparative HPLC to yield acrude oil, which was dissolved in ethyl acetate (10 mL), and treatedwith 1M HCl in ether (5 mL). The resulting precipitation was filtered,washed with methanol (2×20 mL), and dried to afford 122 mg (12% yield)of3-amino-6-[3-({[(2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide(122 mg, 15% yield).: ¹H NMR (400 MHz, DMSO-d6): δ 8.98 (s, 1H), 8.90(m, 1H), 8.75 (s, 1H), 8.63 (m, 2H), 8.11 (m, 1H), 7.95 (m, 2H), 7.62(m, 2H), 7.58 (m, 1H), 7.42 (m, 1H), 7.20 (m, 3H), 7.08 (m, 1H), 5.50(m, 1H), 4.51 (m, 1H), 4.49 (m, 1H), 4.46 (m, 1H), 4.40 (m, 1H), 3.50(m, 1H), 3.65 (m, 2H), 3.20 (m, 2H), 2.85 (m, 1H), 2.10 (m, 1H), 1.80(m, 2H), 1.58 (m, 1H); MS (EI) for C₃₄H₃₆N₆O₃: 577.08 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamidewas prepared using the same synthetic procedure as above followed byhydrogenation (1 atm) with 10% palladium hydroxide in MeOH: ¹H NMR (400MHz, DMSO-d6): δ 9.18 (bs, 1H), 8.97 (m, 2H), 8.82 (m, 1H), 8.61 (m,2H), 8.33 (m, 1H), 7.92 (m, 1H), 7.70 (bs, 2H), 7.59 (t, 1H), 7.27 (m,2H), 7.20 (m, 1H), 5.50 (m, 1H), 4.53 (m, 1H), 4.35 (m, 1H), 3.27 (m,1H), 3.09 (m, 2H), 1.98 (m, 1H), 1.84 (m, 4H), 1.57 (m, 2H); MS (EI) forC₂₇H₃₀N₆O₃: 487.07 (MH⁺).

1,1-dimethylethyl(3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}azepane-1-carboxylate:(3S)-3-aminoazepan-2-one is prepared by either the resolution of racemicα-amino-ε-caprolactam (Sigma-Aldrich) by the method of E. M. Rezler, R.R. Fenton, W. J. Esdale, M. J. McKeage, P. J. Russell, and T. W. HambleyJ. Med. Chem. 1997, 40, 3508-3515, or by chiral synthesis from L-lysineusing the method of R. Pellegata, M. Pinza, and G. Pifferi, Synthesis,1978, 614-616. (3S)-3-[(Triphenylmethyl)amino]azepan-2-one and(3S)-N-(triphenylmethyl)azepan-3-amine were prepared using similarmethods.

1,1-dimethylethyl (3S)-3-[(triphenylmethyl)amino]azepane-1-carboxylate:To an ice-cooled, stirred solution of(3S)-N-(triphenylmethyl)azepan-3-amine (30.0 mmol) in 60 mL of THF, wasadded 9.85 g (45.1 mmol, 1.5 eq.) of di-tert-butyl dicarbonate. The icebath was removed, and the reaction stirred at room temperature for 19 hand concentrated. The crude oil was purified by silica gelchromatography (55 mm column, 7.5 inches of silica gel) using 10% EtOAcin hexanes as eluent. Concentration afforded 13.7 g (100% yield) ofproduct as a solid.

1,1-dimethylethyl (3S)-3-aminoazepane-1-carboxylate: To 13.7 g (30 mmol)of 1,1-dimethylethyl(3S)-3-[(triphenylmethyl)amino]azepane-1-carboxylate was carefully added100 mL MeOH, 75 mL EtOH, and 1.00 g of 10% Palladium on charcoal. Themixture was hydrogenated on a Parr shaker under 30 psi of hydrogen gasfor 15 h. The mixture was filtered through a pad of celite, and thefiltrate concentrated to afford a quantitative yield (6.43 g) ofproduct. The product was used as such without further purification.

1,1-dimethylethyl(3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}azepane-1-carboxylate:A flask was charged with 6.43 g (30 mmol) of 1,1-dimethylethyl(3S)-3-aminoazepane-1-carboxylate, 109 mL THF, 5.49 g of3-amino-6-bromopyrazine-2-carboxylic acid (25.2 mmol, 0.84 eq.), 5.00 mLTEA (35.9 mmol, 1.20 eq.), 5.11 g (37.8 mmol, 1.26 eq.) of1-hydroxybenzotriazole (HOBT), and 7.25 g (37.8 mmol, 1.26 eq.) of1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCI).The reaction was allowed to stir for 16 h. The reaction was diluted withEtOAc, washed with 2×sat. aqueous NaHCO₃, 1×sat. aqueous NaCl, dried(Na₂SO₄), filtered, and concentrated. The crude material was purified bysilica gel chromatography on a 55 mm column (7.5 inches of silica gel)using 30-50% EtOAc in hexanes as eluent. Concentration afforded 4.57 g(43.8% yield) of product as a solid.

The 1,1-dimethylethyl(3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}azepane-1-carboxylatecould be used in a manner analogous to that used for 1,1-dimethylethyl(3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylateto prepare compounds that are part of the invention.

Using the same or analogous synthetic techniques and/or substitutingwith alternative reagents, the following azepan compounds of theinvention were prepared:

3-Amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]phenyl}-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.20 (d, 1H), 8.95 (m, 3H), 8.85 (s, 1H),8.50 (d, 1H), 7.97 (m, 1H), 7.50 (m, 3H), 7.41 (m, 1H), 7.32 (m, 4H),7.05 (m, 1H), 5.60 (m, 1H), 4.35 (m, 1H), 4.29 (m, 1H), 4.20 (m, 1H),3.08 (m, 2H), 2.91 (m, 2H), 2.45 (m, 1H), 2.31 (m, 1H), 1.80 (m, 3H),1.42 (m, 1H), MS (EI) for C₃₄H₃₆N₆O₂: 461.07 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.64 (bs, 1H), 9.32 (bs, 1H), 9.21 (d, 1H),8.98 (m, 2H), 8.70 (bs, 1H), 8.39 (d, 1H), 7.93 (d, 1H), 7.58 (t, 1H),7.30 (m, 4H), 5.62 (m, 1H), 4.35 (m, 1H), 3.21 (m, 2H), 3.18 (m, 1H),3.02 (m, 2H), 2.85 (m, 1H), 2.43 (m, 1H), 2.18 (m, 1H), 1.93 (m, 1H),1.80 (m, 4H), 1.55 (m, 1H); MS (EI) for C₂₇H₃₀N₆O₂: 471.10 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-(3-methylphenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, CD₃OD): δ 8.60 (s, 1H), 7.88 (m, 2H), 7.37 (m, 1H),7.23 (m, 1H), 4.45 (m, 1H), 3.40 (m, 4H), 2.43 (s, 3H), 2.21 (m, 1H),2.00 (m, 2H), 1.65 (m, 1H), 1.32 (m, 1H), 0.98 (m, 1H); MS (EI) forC₁₈H₂₃N₅O: 326.28 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.50 (m, 2H), 9.15 (bs, 1H), 9.02 (d, 1H),8.92 (s, 1H), 8.73 (s, 1H), 8.31 (d, 1H), 7.86 (d, 1H), 7.56 (t, 1H),7.45 (m, 2H), 7.25 (m, 1H), 4.94 (bs, 2H), 4.49 (m, 2H), 4.40 (m, 1H),3.33 (m, 2H), 3.23 (m, 1H), 3.00 (m, 1H), 2.08 (m, 1H), 1.80 (m, 3H),1.55 (m, 1H); MS (EI) for C₂₅H₂₆N₆O₂FCl: 497.03 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.30 (t, 1H), 8.98 (m, 2H), 8.70 (m, 2H),8.59 (s, 1H), 8.32 (s, 1H), 7.89 (d, 1H), 7.72 (bs, 1H), 7.58 (t, 1H),7.34 (m, 1H), 7.20 (m, 2H), 4.60 (m, 2H), 4.36 (m, 1H), 3.35 (m, 1H),3.22 (m, 1H), 3.09 (m, 1H), 2.67 (m, 1H), 2.33 (m, 1H), 1.99 (m, 1H),1.85 (m, 3H), 1.58 (m, 1H); MS (EI) for C₂₅H₂₆N₆O₂F₂: 481.08 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.48 (m, 1H), 9.37 (m, 1H), 8.99 (m, 2H),8.95 (s, 1H), 8.32 (d, 1H), 7.85 (d, 1H), 7.55 (t, 1H), 7.43 (m, 2H),7.23 (m, 1H), 4.50 (m, 3H), 3.34 (m, 2H), 3.24 (m, 2H), 3.07 (m, 1H),2.05 (m, 1H), 1.80 (m, 4H), 1.58 (m, 1H); MS (EI) for C₂₅H₂₆N₆O₂F₂:481.08 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.46 (t, 2H), 9.18 (bs, 1H), 8.95 (m, 3H),8.68 (s, 1H), 8.33 (m, 1H), 7.91 (d, 1H), 7.70 (bs, 1H), 7.60 (t, 1H),7.12 (m, 3H), 4.54 (m, 2H), 4.39 (m, 1H), 3.38 (m, 2H), 3.24 (m, 1H),3.06 (m, 1H), 2.00 (m, 1H), 1.89 (m, 4H), 1.57 (m, 1H); MS (EI) forC₂₅H₂₆N₆O₂F₂: 481.07(MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.58 (bs, 1H), 9.30 (m, 1H), 9.23 (bs, 1H),9.00 (d, 1H), 8.93 (s, 1H), 8.63 (s, 1H), 8.52 (bs, 2H), 8.33 (m, 1H),7.86 (m, 1H), 7.79 (m, 1H), 7.60 (m, 2H), 7.32 (t, 1H), 7.18 (t, 1H),4.58 (m, 2H), 4.41 (m, 1H), 4.06 (m, 2H), 3.31 (m, 1H), 3.22 (m, 2H),3.01 (m, 1H), 2.00 (m, 1H), 1.90 (m, 2H), 1.80 (m, 2H), 1.59 (m, 1H); MS(EI) for C₂₅H₂₅N₆O₂F₂Cl: 515.03 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.48 (bs, 1H), 9.38 (m, 1H), 9.14 (bs, 1H),9.10 (m, 1H), 8.95 (s, 1H), 8.69 (s, 1H), 8.32 (m, 1H), 7.89 (m, 1H),7.57 (m, 1H), 6.83 (s, 3H), 4.41 (m, 2H), 3.45 (m, 4H), 3.17 (m, 1H),2.00 (m, 1H), 1.89 (m, 3H), 1.59 (m, 1H); MS (EI) for C₂₇H₃₀N₆O₄:503.10. (MH⁺)

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.34 (bs, 1H), 9.09 (m, 1H), 8.97 (d, 1H),8.92 (s, 1H), 8.60 (s, 2H), 8.55 (bs, 2H), 8.34 (m, 1H), 7.85 (m, 1H),7.54 (m, 2H), 7.44 (m, 1H), 7.39 (m, 2H), 7.25 (m, 1H), 4.63 (m, 2H),4.40 (m, 1H), 3.25 (m, 2H), 3.03 (m, 1H), 2.00 (m, 1H), 1.90 (m, 1H),1.83 (m, 2H), 1.59 (m, 1H); MS (EI) for C₂₅H₂₆N₆O₂FCl: 497.31 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.20 (bs, 1H), 9.05 (m, 1H), 8.97 (bs, 1H),8.90 (s, 1H), 8.82 (m, 1H), 8.51 (s, 1H), 8.30 (m, 1H), 7.83 (m, 1H),7.69 (bs, 1H), 7.53 (t, 1H), 7.36 (m, 1H), 7.10 (m, 2H), 4.55 (m, 2H),4.34 (m, 1H), 3.25 (m, 3H), 3.06 (m, 2H), 1.90 (m, 1H), 1.83 (m, 3H),1.57 (m, 1H); MS (EI) for C₂₅H₂₆N₆O₂F₂: 481.29 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.46 (m, 1H), 9.27 (bs, 1H), 8.94 (m, 2H),8.92 (s, 1H), 8.67 (m, 1H), 8.30 (d, 1H), 7.70 (bs, 1H), 7.60 (m, 2H),7.56 (m, 2H), 7.36 (m, 2H), 4.50 (m, 3H), 3.32 (m, 2H), 3.22 (m, 2H),3.03 (m, 1H), 2.01 (m, 1H), 1.85 (m, 3H), 1.59 (m, 1H); MS (EI) forC₂₅H₂₆N₆O₂FCl: 497.25 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d6): δ 9.36 (m, 1H), 9.14 (m, 1H), 8.92 (s, 1H),8.87 (m, 2H), 8.62 (m, 1H), 8.10 (m, 1H), 7.88 (m, 2H), 7.57 (t, 1H),7.48 (m, 1H), 7.39 (m, 1H), 7.19 (m, 1H), 4.57 (m, 1H), 4.36 (bs, 1H),3.23 (m, 1H), 3.04 (m, 1H), 1.99 (m, 1H), 1.90 (m, 3H), 1.79 (m, 1H),1.57 (m, 1H); MS (EI) for C₂₅H₂₆N₆O₂FCl: 497.04 (MH⁺).

Example 70

Scheme 26 depicts another strategy for making exemplary compoundsaccording to formula I where A is a triazole. Nitrile intermediates(cvi) were converted to aminoamidines (cvii), which were acylated andthe intermediates cyclized to form

3-{5-Amino-6-[imino(2-methylhydrazino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.21-9.15 (m, 1H), 8.95-8.91 (m, 1H), 8.54(s, 1H), 8.31 (bs, 1H), 7.93-7.88 (m, 1H), 7.93-7.42 (bs, 2H), 7.62-7.55(m, 1H), 7.38-7.31 (m, 4H), 7.29-7.23 (m, 1H), 4.57-4.51 (m, 1H), 2.89(bs, 3H); MS (EI) for C₂₀H₂₁N₇O: 376.16 (MH⁺).

3-{5-Amino-6-[imino(2-phenylhydrazino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.21-9.15 (m, 1H), 8.74 (bs, 2H), 8.55-8.51(m, 1H), 8.31-8.25 (m, 1H), 7.89-7.84 (m, 1H), 7.59-7.52 (m, 1H),7.37-7.20 (m, 6H), 6.98-6.92 (m, 2H), 6.80-6.71 (m, 1H), 4.57-4.50 (m,2H); MS (EI) for C₂₅H₂₃N₇O: 438.15 (MH⁺).

3-{5-Amino-6-[imino(morpholin-4-ylamino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.21-9.14 (m, 1H), 8.90 (bs, 1H), 8.75 (s,1H), 8.53-8.49 (m, 1H), 8.28-8.23 (m, 1H), 7.88-7.83 (m, 1H), 7.58-7.51(m, 1H), 7.50-7.00 (m, 6H), 6.65 (bs, 2H), 4.56-4.49 (m, 2H), 3.80-3.71(m, 4H), 2.80-2.65 (m, 4H); MS (EI) for C₂₃H₂₅N₇O₂: 432.15 (MH⁺).

3-(5-Amino-6-{imino[(4-methylpiperazin-1-yl)amino]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.80 (bs, 2H), 9.20-9.12 (m, 1H), 8.86 (bs,1H), 8.50 (s, 1H), 8.22 (bs, 1H), 7.91-7.86 (m, 1H), 7.60-7.53 (m, 1H),7.36-7.20 (m, 5H), 4.56-4.48 (m, 2H), 3.40-3.15 (m, 4H), 2.92-2.75 (m,7H); MS (EI) for C₂₄H₂₈N₈O: 445.18 (MH⁺).

3-{5-Amino-6-[imino(piperidin-1-ylamino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.21-9.14 (m, 1H), 8.98 (bs, 1H), 8.73 (s,1H), 8.53-8.49 (m, 1H), 8.27-8.22 (m, 1H), 7.88-7.83 (m, 1H), 7.58-7.51(m, 1H), 7.38-7.18 (m, 5H), 6.51 (bs, 2H), 4.56-4.49 (m, 2H), 2.74-2.60(m, 4H), 1.74-1.62 (m, 4H), 1.50-1.38 (m, 2H); MS (EI) for C₂₄H₂₇N₇O:430.18 (MH⁺).

3-{5-Amino-6-[(azepan-1-ylamino)(imino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 11.23 (bs, 1H), 9.80 (bs, 1H), 9.17-9.08(m, 2H), 8.92 (s, 1H), 8.49-8.43 (m, 1H), 8.16-8.08 (m, 1H), 7.92-7.86(m, 1H), 7.60-7.53 (m, 1H), 7.38-7.05 (m, 6H), 4.57-4.47 (m, 2H),3.15-2.95 (m, 4H), 1.85-1.55 (m, 8H); MS (EI) for C₂₅H₂₉N₇O: 444.20(MH⁺).

3-{5-Amino-6-[imino({(2R)-2-[(methyloxy)methyl]pyrrolidin-1-yl}amino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.79 (bs, 1H), 9.37 (bs, 1H), 9.16-9.10 (m,1H), 8.95 (s, 1H), 8.50-8.46 (m, 1H), 8.17-8.10 (m, 1H), 7.92-7.87 (m,1H), 7.61-7.54 (m, 1H), 7.38-7.18 (m, 5H), 7.04 (bs, 2H), 4.55-4.48 (m,2H), 3.55-3.48 (m, 2H), 3.42-3.32 (m, 1H), 3.28 (s, 3H), 3.27-3.18 (m,1H), 2.85-2.74 (m, 1H), 2.10-1.72 (m, 4H), 1.54-1.38 (m, 1H); MS (EI)for C₂₅H₂₉N₇O₂: 460.18 (MH⁺).

3-[5-Amino-6-(imino{2-[4-(trifluoromethyl)pyrimidin-2-yl]hydrazino}methyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.25-9.05 (m, 2H), 8.99 (s, 1H), 8.79 (bs,1H), 8.47-8.43 (m, 1H), 8.14-8.08 (m, 1H), 7.95-7.90 (m, 1H), 7.62-7.41(m, 4H), 7.39-7.21 (m, 6H), 6.91 (bs, 1H), 4.55-4.50 (m, 2H); MS (EI)for C₂₄H₂₀N₉OF₃: 508.09 (MH⁺).

3-[5-Amino-6-(1,5-diphenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20-9.13 (m, 1H), 8.84 (s, 1H), 8.56-8.52(m, 1H), 8.25-8.20 (m, 1H), 7.91-7.85 (m, 1H), 7.60-7.38-7.30 (m, 5H),7.28-7.22 (m, 1H), 4.55-4.50 (m, 2H); MS (EI) for C₃₂H₂₅N₇O: 524.12(MH⁺).

3-[5-Amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.21-9.14 (m, 1H), 8.75 (s, 1H), 8.54-8.50(m, 1H), 8.22-8.17 (m, 1H), 7.90-7.85 (m, 1H), 7.62-7.55 (m, 2H),7.40-7.20 (m, 6H), 4.57-4.50 (m, 2H), 3.94 (s, 3H), 2.55 (s, 3H); MS(EI) for C₂₂H₂₁N₇O: 400.16 (MH⁺).

3-[5-Amino-6-(1-methyl-5-phenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.22-9.13 (m, 1H), 8.79 (s, 1H), 8.56-8.52(m, 1H), 8.24-8.19 (m, 1H), 7.95-7.86 (m, 3H), 7.68-7.51 (m, 5H),7.40-7.21 (m, 6H), 4.57-4.48 (m, 2H), 4.13 (s, 3H); MS (EI) forC₂₇H₂₃N₇O: 462.11 (MH⁺).

3-{5-Amino-6-[imino(2-pyridin-2-ylhydrazino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.46 (bs, 1H), 9.26-9.19 (m, 1H), 8.74 (s,1H), 8.59-8.55 (m, 1H), 8.36-8.30 (m, 1H), 8.16-8.12 (m, 1H), 7.91-7.86(m, 1H), 7.70-7.62 (m, 1H), 7.60-7.53 (m, 1H), 7.40-7.32 (m, 4H),7.30-7.22 (m, 1H), 6.90-6.82 (m, 1H), 6.79-6.70 (m, 3H), 4.59-4.53 (m,2H); MS (EI) for C₂₄H₂₂N₈O: 439.15 (MH⁺).

3-[5-Amino-6-(1-methyl-5-piperidin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.42-9.23 (m, 2H), 9.21-9.13 (m, 1H), 8.79(s, 1H), 8.52-8.48 (m, 1H), 8.20-8.14 (m, 1H), 7.92-7.86 (m, 1H),7.68-7.54 (m, 2H), 7.39-7.31 (m, 4H), 7.30-7.22 (m, 1H), 4.92-4.81 (m,1H), 4.57-4.49 (m, 2H), 4.06 (s, 3H), 3.22-3.02 (m, 2H), 2.23-2.14 (m,1H), 1.95-1.60 (m, 5H); MS (EI) for C₂₆H₂₈N₈O: 469.17 (MH⁺).

3-[5-Amino-6-(5-methyl-1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.22-9.15 (m, 1H), 8.82 (s, 1H), 8.66-8.61(m, 1H), 8.56-8.53 (m, 1H), 8.25-8.20 (m, 1H), 8.17-8.11 (m,1H),8.10-8.05 (m, 1H), 7.92-7.87 (m, 1H), 7.63-7.52 (m, 4H), 7.39-7.31 (m,4H), 7.29-7.22 (m, 1H), 4.57-4.50 (m, 2H), 2.90 (s, 3H); MS (EI) forC₂₆H₂₂N₈O: 463.15 (MH⁺).

3-{5-Amino-6-[(2-ethylhydrazino)(imino)methyl]pyrazin-2-yl}-N-(2,3-dihydro-1H-inden-1-yl)benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.8 (s, 1H), 8.7 (s, 1H), 8.2 (m, 1H), 7.80(m, 1H), 7.4 (m, 2H), 7.2 (m, 3H), 5.8 (m, 1H), 2.8 (m, 2.4 (m, 2H), 2.0(m, 2H), 1.5 (m, 3H). MS (EI) for C₂₃H₂₅N₇O: 416 (MH⁺).

3-{5-Amino-6-[imino(2-methylhydrazino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.96-8.91 (m, 1H), 8.64 (s, 1H), 8.53-8.50(m, 1H), 8.30-8.24 (m, 1H), 7.92-7.87 (m, 1H), 7.58-7.52 (m, 1H),7.32-7.17 (m, 4H), 6.03 (s, 2H), 5.67-5.58 (m, 1H), 5.26 (s, 1H),3.08-2.96 (m, 1H), 2.94-2.85 (m, 1H), 2.84 (s, 3H), 2.50-2.44 (m, 1H),2.07-1.99 (m, 1H). MS (EI) for C₂₂H₂₃N₇O: 402 (MH⁺).

3-{5-Amino-6-[imino(2-phenylhydrazino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.00-8.91 (m, 1H), 8.78-8.68 (m, 1H),8.57-8.53 (m, 1H), 8.36-8.30 (m, 1H), 7.95-7.89 (m, 1H), 7.61-7.52 (m,1H), 7.33-7.14 (m, 5H), 6.99-6.93 (m, 2H), 6.78-6.71 (m, 1H), 6.50 (s,2H), 5.68-5.57 (m, 1H), 3.08-2.96 (m, 1H), 2.95-2.82 (m, 1H), 2.56-2.46(m, 1H), 2.10-1.97 (m, 1H). MS (EI) for C₂₇H₂₅N₇O: 464 (MH⁺).

Phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.93-8.88 (m, 1H), 8.74 (s, 1H), 8.53-8.49(m, 1H), 8.20-8.14 (m, 1H), 7.93-7.85 (m, 1H), 7.61-7.54 (m, 1H),7.42-7.15 (m, 11H), 5.67-5.57 (m, 1H), 5.10 (s, 2H), 4.18-3.88 (m, 6H),2.12-1.93 (m, 2H), 1.88-1.70 (m, 2H), 1.64-1.42 (m, 2H). MS (EI) forC₃₆H₃₆N₈O₃: 629 (MH⁺).

Phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate:¹H NMR (400 MHz, d₄-MeOH): δ 8.8 (s, 1H), 8.7 (s, 1H), 8.2 (m, 1H), 7.80(m, 1H), 7.4 (m, 2H), 7.3 (m, 5H), 7.2 (m, 3H), 5.8 (m, 1H), 2.8 (m,2H), 2.4 (m, 2H), 2.2-3.2 (m, 7H), 1.8-2.0 (m, 9H). MS (EI) forC₃₇H₃₈N₈O₃: 643 (MH⁺).

3-Amino-6-bromo-N′-pyridin-2-ylpyrazine-2-carboximidohydrazide: ¹H NMR(400 MHz, d₆-DMSO): δ 9.00 (s, 1H), 8.95 (m, 1H), 8.55 (s, 1H), 8.10 (d,1H), 7.95 (d, 1H), 7.50 (m, 3H), 7.30-7.10 (m, 4H), 5.60 (m, 2H),3.0-2.8 (m, 2H), 2.40 (m, 1H), 2.00 (m, 1H). MS (EI) for C₁₀H₁₀BrN₇:356(MH⁺).

3-[5-Amino-6-(1-ethyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(2,3-dihydro-1H-inden-1-yl)benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.8 (s, 1H), 8.7 (s, 1H), 8.2 (m, 1H), 7.80(m, 1H), 7.4 (m, 2H), 7.2 (m, 3H), 5.8 (m, 1H), 2.8 (m, 2H), 2.4 (m,2H), 2.2-3.2 (m, 5H), 1.8-2.0 (m, 9H). MS (EI) for C₂₉H₃₂N₈O: 509 (MH⁺).

3-[5-Amino-6-(1-methyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.57-8.49 (m, 2H), 8.12-8.05 (m, 1H),7.89-7.82 (m, 1H), 7.54-7.46 (m, 1H), 7.28-7.06 (m, 4H), 5.67-5.56 (m,1H), 3.96 (s, 3H), 3.57-3.24 (m, 3H), 3.10-2.87 (m, 3H), 2.60-2.46 (m,1H), 2.15-1.40 (m, 6H). MS (EI) for C₂₈H₃₀N₈O: 495 (MH⁺).

3-{5-Amino-6-[imino(2-pyridin-4-ylhydrazino)methyl]pyrazin-2-yl}-N-(2,3-dihydro-1H-inden-1-yl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 10.9 (s, 1H), 8.95 (m, 2H), 8.55 (s, 1H),8.30-8.10 (m, 3H), 7.95-7.00 (m, 10H), 5.60 (m, 2H), 3.0-2.8 (m, 2H),2.40 (m, 1H), 2.00 (m, 1H). MS (EI) for C₂₆H₂₄N₈O: 465 (MH⁺).

Phenylmethyl3-[3-(3-amino-6-bromopyrazin-2-yl)-1-pyridin-2-yl-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate:¹H NMR (400 MHz, d₄-MeOH): δ 8.20 (s, 1H), 7.40-7.20 (m, 9H), 5.10 (m,2H), 4.00-3.60 (m, 4H), 3.2 (m, 1H), 2.0-1.40 (m, 4H). MS (EI) forC₂₄H₂₃BrN₈O₈: 536 (MH⁺).

Phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate:¹H NMR (400 MHz, d₄-MeOH): δ 8.8 (s, 1H), 8.7 (s, 1H), 8.2 (m, 1H), 7.80(m, 1H), 7.4 (m, 2H), 7.3 (m, 5H), 7.2 (m, 3H), 5.8 (m, 1H), 2.8 (m,2H), 2.4 (m, 2H), 2.2-3.2 (m, 7H), 1.8-2.0 (m, 9H). MS (EI) forC₃₇H₃₈N₈O₃: 643 (MH⁺).

3-(5-Amino-6-(1-ethyl-5-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.8 (s, 1H), 8.7 (s, 1H), 8.2 (m, 1H), 7.80(m, 1H), 7.4 (m, 2H), 7.2 (m, 3H), 5.8 (m, 1H), 2.8 (m, 2H), 2.4 (m,2H), 2.2-3.2 (m, 5H), 1.8-2.0 (m, 9H). MS (EI) for C₂₉H₃₂N₈O: 509 (MH⁺).

Phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate¹HNMR (400 MHz, d₄-MeOH): δ 8.95 (m, 1H), 8.60 (m, 1H), 8.20 (d, 1H), 7.95(d, 1H), 7.60 (m, 1H), 7.40-7.20 (m, 9H), 5.65 (m, 1H), 5.20 (m, 2H),4.2-3.8 (m, 4H), 3.20-2.80 (m, 5H), 2.60 (m, 1H), 2.20-1.60 (m, 5H). MS(EI) for C₃₆H₃₆N₈O₃: 629 (MH⁺).

3-[5-Amino-6-(5-{2-[(phenylmethyl)oxy]ethyl}-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.8 (s, 1H), 8.7 (s, 1H), 8.2 (m, 1H), 7.80(m, 1H), 7.4 (m, 2H), 7.25 (m, 5H), 7.2 (m, 3H), 5.8 (m, 1H), 3.0 (m,4H), 2.8 (m, 2H), 2.4 (m, 2H), 2.0 (m, 2H). MS (EI) for C₃₁H₂₉N₇O₂: 532(MH⁺).

3-[5-Amino-6-(1-phenyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.72-8.61 (m, 2H), 8.22-8.17 (m, 1H),7.97-7.91 (m, 1H), 7.70-7.56 (m, 6H), 7.36-7.15 (m, 4H), 5.76-5.66 (m,1H), 3.58-3.46 (m, 2H), 3.15-2.86 (m, 4H), 2.68-2.57 (m, 1H), 2.15-1.75(m, 6H). MS (EI) for C₃₃H₃₂N₈O: 557 (MH⁺).

3-{5-Amino-6-[amino(imino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (m, 2), 8.50 (s, 1H), 8.20 (d, 1H),7.95 (d, 1H), 7.60 (m, 1H), 7.40-7.20 (m, 4H), 5.60 (m, 1H), 3.20-2.80(m, 2H), 2.20-2.00 (m, 2H). MS (EI) for C₂₁H₂₀N₆O: 373 (MH⁺).

3-[5-Amino-6-(5-methyl-1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.00-8.90 (m, 3H), 8.50 (s, 1H), 8.20 (d,1H), 7.95 (m, 2H), 7.60 (m, 2H), 7.40-7.20 (m, 4H), 5.60 (m, 1H),3.20-2.80 (m, 2H), 2.75 (s, 3H), 2.20-2.00 (m, 2H). MS (EI) forC₂₈H₂₄N₈O: 489 (MH⁺).

3-[5-Amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.75 (m, 2H), 8.20 (d, 1H), 7.95 (d, 1H),7.60 (m, 1H), 7.40-7.20 (m, 4H), 5.70 (m, 1H), 4.00 (s, 3H), 3.20-2.80(m, 2H), 2.60 (s, 3H), 2.20-2.00 (m, 2H). MS (EI) for C₂₄H₂₃N₇O: 426(MH⁺).

3-[5-Amino-6-(1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S-2,3-dihydro-1H-inden-1-yl]benzamide:¹H NMR (400 MHz, d₄-MeOH): δ 9.00 (s, 1H), 8.95 (m, 1H), 8.60 (s, 1H),8.25 (d, 1H), 8.20-8.00 (m, 3H), 7.90-7.60 (m, 4H), 7.40-7.00 (m, 3H),5.80 (m, 1H), 3.20-2.60 (m, 3H), 2.20-2.00 (m, 1H). MS (EI) forC₂₇H₂₂N₈O: 475 (MH⁺).

Example 71

Scheme 27 depicts another strategy for making exemplary compoundsaccording to formula I where A is a pyrimidine. Weirireb's amideintermediates (cix) were converted to α,β-unsaturated intermediates(cx), which were coupled with amindines and the intermediates cyclizedto form pyrimidines (cxi). Intermediate (cix) can also be used to makeother heterocycles for A, according to formula I.

3-[5-Amino-6-(2-aminopyrimidin-4-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:To a THF (50 mL) solution of3-amino-6-{3-[(benzylamino)carbonyl]phenyl}-N-methoxy-N-methylpyrazine-2-carboxamide(1.0 g, 2.6 mmol) was added 3.0 M methylmagnesium chloride in THF (6.1mL, 18 mmol) and the mixture was stirred for 3 h. Saturated ammoniumchloride was added and the mixture was extracted 3× with ethyl acetate.The combined organic layers were dried over sodium sulfate, filtered,and concentrated under reduced pressure. The crude product was purifiedby silica gel chromatography to afford the pure methyl ketone (0.400 g,45% yield). This material was dissolved in ethanol (20 mL),dimethylformamide dimethyl acetal (2 mL, 15 mmol) was added and themixture was heated to reflux for 90 min. LCMS analysis showed desiredproduct and complete consumption of starting material. The reactionmixture was concentrated under reduced pressure and redissolved inethanol (10 mL). Guanidine (0.364 g, 2.0 mmol) was added followed bypotassium carbonate (0.80 g, 5.8 mmol). The mixture was heated in asealed tube at 80° C. overnight. The mixture was transferred to around-bottomed flask and concentrated under reduced pressure. Water (100mL) was added and the residue was extracted with ethyl acetate (3×100mL). The combined organic fractions were washed with water, dried overanhydrous sodium sulfate, filtered and concentrated under reducedpressure to give the desired product (0.103 g, 45% yield). ¹H NMR (400MHz, d₆-DMSO): δ 9.22 (br s, 1H), 8.86 (s, 1H), 8.56 (m, 1H), 8.40 (d,1H), 8.25 (d, 1H), 7.90 (d, 1H), 7.71 (d, 1H), 7.59 (t, 1H), 7.52 (br s,1H), 7.36 (m, 4H), 7.26 (m, 1H), 7.01 (br s, 1H), 4.53 (m, 3H). MS (EI)for C₂₂H₁₉N₇O: 398 (MH⁺).

Using the same or similar synthetic techniques, substituting with theappropriate reagents such as the respective amines, the followingcompounds of the invention were prepared:

3-{5-Amino-6-[2-(dimethylamino)pyrimidin-4-yl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (t, 1H), 8.80 (s, 1H), 8.57 (s, 1H),8.54 (d, 1H), 8.26 (d, 1H), 7.90 (d, 1H), 7.75 (d, 1H), 7.59 (t, 1H),7.36 (m, 4H), 7.26 (m, 1H), 4.58 (m, 1H), 4.54 (d, 2H), 3.20 (s, 6H). MS(EI) for C₂₄H₂₃N₇O: 426 (MH⁺).

3-[5-Amino-6-(2-methylpyrimidin-4-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (t, 1H), 8.92 (s, 1H), 8.88 (d, 1H),8.59 (s, 1H), 8.43 (d, 1H), 8.39, (m, 1H), 8.30 (d, 1H), 7.92 (d, 1H),7.60 (t, 1H), 7.36 (m, 5H), 7.28 (m, 1H), 4.58 (t, 1H), 4.54 (d, 2H),2.77 (s, 3H). MS (EI) for C₂₃H₂₀N₆O: 397 (MH⁺).

3-{5-Amino-6-[2-(methylamino)pyrimidin-4-yl]pyrazin-2-yl}-N-(phenylmethyl)benzamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.20 (br s, 1H), 8.86 (m, 1H), 8.56 (m,1H), 8.45 (m, 1H), 8.25 (m, 1H), 7.89 (m, 1H), 7.72 (m, 1H), 7.60 (m,1H), 7.35 (m, 4H), 7.27 (m, 2H), 4.54 (m, 3H), 2.87 (m, 3H). MS (EI) forC₂₃H₂₁N₇O: 412 (MH⁺).

Example 72

Scheme 28 depicts another strategy for making exemplary compoundsaccording to formula I where W is a substituted phenylene. Analogous todimerization described in Example 51, Scheme 17, above, intermediates(cxiii) were prepared by coupling aryl halides such as (cxii) toappropriate pyrazines, as depicted. In this example, mono-saponificationof the esters and thus selective amide formation gave compounds (cxiv).The saponification process was repeated to make compounds (cxv).

Dimethyl5-{5-amino-6-[(methyloxy)carbonyl]pyrazin-2-yl}benzene-1,3-dicarboxylate:A mixture containing 5-bromoisophthalic acid dimethyl ester (0.20 g,0.73 mmol), bispinacolatodiboron (0.21 g, 0.80 mmol),1,1′-bis(diphenylphosphine)ferrocene palladium dichloride (0.029 g,0.035 mmol), and potassium acetate (0.26 g, 2.3 mmol) in dioxane (5 mL)was heated at 80° C. for 1 h. The reaction mixture was cooled to roomtemperature and methyl 3-amino-6-bromo-pyrazine-2-carboxylate (0.17 mg,0.70 mmol), 1,1′-bis(diphenylphosphine)ferrocene palladium dichloride(0.035 g, 0.042 mmol), sodium bicarbonate (320 mg, 3.8 mmol), and water(1 mL) were added. The mixture was heated at 80° C. for 12 h, afterwhich time, the mixture was diluted with water and ethyl acetate. Thelayers were separated and the organic layer was extracted with 1 Nhydrochloric acid (2×) and dried over sodium sulfate. Filtration,concentration, and silica gel chromatography gave the product as ayellow solid (23 mg, 12% yield). ¹H NMR (400 MHz, d₆-DMSO): δ 9.04 (s,1H), 8.74 (d, 2H), 8.44 (t, 1H), 7.62 (s, 2H), 3.32 (s, 3H), 2.49 (s,3H), 2.48 (s, 3H). MS (EI) for C₁₆H₁₅N₃O₆: 346 (MH⁺).

3-{5-Amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-[(methyloxy)carbonyl]benzoicacid: A mixture containing dimethyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzene-1,3-dicarboxylate(1.1 g, 3.2 mmol) and aqueous sodium hydroxide (3 mL of a 1N solution)was heated in dioxane (100 mL) at 95° C. for 3 h. The mixture wasdiluted with 1 N aqueous hydrochloric acid (300 mL) and extracted withethyl acetate (3×300 mL) and saturated ammonium chloride solution anddried over sodium sulfate. Filtration, concentration and purification byreverse phase HPLC gave the product as a yellow solid (0.39 g, 37%yield). ¹H NMR (400 MHz, d₆-DMSO): δ 8.83 (s, 1H), 8.78 (d, 1H), 8.70(d, 2H), 8.39 (t, 1H), 7.69 (br, 2H), 6.47 (br, 1H), 3.87 (s, 3H), 2.79(d, 3H). MS (EI) for C₁₅H₁₄N₄O₅: 331 (MH⁺).

Methyl3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}benzoate:A mixture containing3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-[(methyloxy)carbonyl]benzoicacid (0.34 g, 1.0 mmol),O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate(0.51 g, 1.6 mmol), (S)-(+)-1-aminoindan (0.17 g, 1.3 mmol),diisopropylethylamine (0.6 mL, 3.4 mmol) and DMF (70 mL) were stirred atroom temperature for 12 h. The reaction mixture was diluted with waterand extracted 3' with ethyl acetate and 3× with 5% aqueous lithiumchloride, and dried over sodium sulfate. Filtration, concentration, andpurification by reverse phase HPLC gave the product as a yellow solid(0.41 g, 90% yield). ¹H NMR (400 MHz, d₆-DMSO): δ 9.09 (d, 1H), 8.91 (s,1H), 8.83 (d, 1H), 8.75 (t, 1H), 8.70 (t, 1H), 8.45 (t, 1H), 7.73 (br,2H), 7.28 (d, 2H), 7.24-7.17 (m, 2H), 5.64-5.58 (q, 1H), 3.91 (s, 3H),3.04-3.00 (m, 1H), 3.00-2.87 (m, 1H), 2.83 (d, 3H), 2.53-2.51 (m, 1H),2.06-1.96 (m, 1H). MS (EI) for C₂₄H₂₃N₅O₄: 446 (MH⁺).

3-Amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]-4-fluorophenyl}-N-methylpyrazine-2-carboxamide:A solution of methyl 2-fluoro-5-iodobenzoate (0.41 g, 1.5 mmol),bispinacolatodiboron (0.41 g, 1.6 mmol), Pd(dppfCl₂).CH₂Cl₂ (180 mg,0.22 mmol) and potassium acetate (0.43 g, 4.4 mmol) was heated at 80° C.in dioxane (50 mL) for 48 h. To this solution was added3-amino-6-bromo-N-methylpyrazine-2-carboxamide (0.35 g, 1.5 mmol),additional Pd(dppfCl₂).CH₂Cl₂ (0.2 g, 0.2 mmol), sodium bicarbonate (0.5g, 6 mmol), and water (5 mL) and the resulting solution was heated at90° C. for an additional 16 h. The cooled solution was filtered throughcelite and concentrated under reduced pressure. Dichloromethane (100 mL)was added to the residue, which was washed with water, brine, and driedover anhydrous sodium sulfate. Filtration, concentration and silica gelchromatography gave the biaryl product (0.24 g, 54% yield) as a lightyellow solid. A solution of this material and lithium hydroxide (160 mg,3.8 mmol) in dioxane (60 mL) and water (5 mL) was heated at 70° C. for 6h. To the cooled solution was added 1M aqueous HCl and the reaction wasconcentrated to approximately 10 mL. The resulting solid was filteredand dried to yield the carboxylic acid (0.22 g, 97% yield) as a yellowsolid. To a solution of this material, (S)-(+)-aminoindane (107 mg, 0.8mmol) and Hunig's base (0.7 mL, 4 mmol) in DMF (10 mL) was added HATU(0.38 g, 1.0 mmol) and the solution was stirred at room temperature for4 h. Ethyl acetate (50 mL) was added to the solution and it was washedwith a 5% aqueous solution of lithium chloride (3×50 mL) and brine,dried over anhydrous sodium sulfate, filtered, and concentrated underreduced pressure to yield a residue that was purified by silica gelchromatography to yield the desired product as a pale yellow solid (64mg, 20% yield). ¹H NMR (400 MHz, CDCl₃): δ 8.69-8.66 (m, 2H), 8.38 (m,1H), 7.99-7.95 (m, 2H), 7.40-7.02 (m, 7H), 5.77-5.75 (m, 1H), 3.07-2.75(m, 6H), 1.99-195 (m, 1H). MS (EI) for C₂₂H₂₀FN₅O₂: 406 (MH⁺).

Using the same or similar synthetic techniques, substituting with theappropriate reagents such as the respective amines, the followingcompounds of the invention were prepared:

3-Amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]-5-fluorophenyl}-N-methylpyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.96-8.93 (m, 3H), 8.39-8.29 (m, 2H),7.66-7.64 (m, 1H), 7.29-7.19 (m, 4H), 5.59 (m, 1H), 3.34-2.84 (m, 6H),2.03-1.98 (m, 1H). MS (EI) for C₂₂H₂₀FN₅O₂: 406 (MH⁺).

Dimethyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzene-1,3-dicarboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.85 (s, 1H), 8.79 (d, 1H), 8.73-8.72 (m,2H), 8.39-8.38 (m, 1H), 7.75 (br, 1H), 3.87 (s, 6H), 3.82 (br, 1H), 2.79(d, 3H). MS (EI) for C₁₆H₁₆N₄O₅: 345 (MH⁺).

1,1-Dimethylethyl(3S)-3-{[(3-amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)sulfonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.80 (s, 1H), 8.59 (d, 1H), 8.40-8.38 (m,2H), 8.08 (br, 1H), 7.79 (t, 1H), 7.67 (br, 1H), 7.66-7.62 (m, 2H),7.10-7.04 (m, 4H), 4.70 (t, 1H), 4.43-4.39 (m, 1H), 3.56-3.47 (m, 1H),3.40-3.34 (m, 1H), 3.24-3.17 (m, 2H), 2.76-2.70 (m, 1H), 2.69-2.53 (m,1H), 2.04-1.89 (m, 3H), 1.63-1.54 (m, 1H), 1.33 (s, 9H). MS (EI) forC₂₉H₃₄N₆O₅S: 577 (MH⁻).

3-Amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)sulfonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 8.86 (s, 1H), 8.69-8.68 (m, 1H), 8.50-8.47(m, 2H), 7.85 (d, 1H), 7.75 (br s, 1H), 7.70 (t, 2H), 7.14 (d, 4H), 4.77(t, 1H), 4.41 (br s, 1H), 3.10-2.99 (m, 2H), 2.86-2.76 (m, 3H),2.68-2.60 (m, 1H), 2.49 (s, 2H), 2.09-2.03 (m, 2H), 1.83-1.75 (m, 1H),1.70-1.61 (m, 1H). MS (EI) for C₂₄H₂₆N₆O₃S: 477 (MH⁺).

1,1-Dimethylethyl-3-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)carbonyl]amino}pyrrolidine-1-carboxylate:¹H NMR (400 MHz, d₆-DMSO): δ 8.95 (d, 1H), 8.88 (s, 1H), 8.80 (d, 1H),8.72 (d, 1H), 8.59 (s, 1H), 8.53 (s, 1H), 8.26 (s, 1H), 7.73 (br, 2H),7.20-7.12 (m, 2H), 5.55 (q, 1H), 4.40 (m, 1H), 3.55-3.50 (m, 1H),3.42-3.35 (m, 1H), 3.25-3.18 (m, 1H), 2.99-2.82 (m, 1H), 2.60 (m, 1H),2.46-2.44 (m, 1H), 2.43 (s, 3H), 2.43-2.26 (m, 1H), 2.10-1.88 (m, 3H),1.34 (s, 9H). MS (EI) for C₃₂H₃₇N₇O₅: 598 (MH⁻).

5-{5-Amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-N′-pyrrolidin-3-ylbenzene-1,3-dicarboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.02 (d, 1H), 8.93 (s, 1H), 8.84-8.80 (m,4H), 8.67 (t, 1H), 8.60 (t, 1H), 8.33 (t, 1H), 7.77 (br s, 2H), 7.28 (d,2H), 7.24-7.17 (m, 2H), 5.60 (q, 1H), 4.57-4.51 (m, 1H), 3.39 (m, 1H),3.32-3.21 (m, 2H), 3.04-2.98 (m, 1H), 2.91-2.87 (m, 1H), 2.84 (d, 3H),2.50 (m, 1H), 2.27-2.18 (m, 1H), 2.10-1.89 (s, 2H). MS (EI) forC₂₇H₂₉N₇O₃: 500 (MH⁺).

5-{5-Amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-(2,3-dihydro-1H-inden-1-yl)-N′-pyrrolidin-3-ylbenzene-1,3-dicarboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.02 (d, 1H), 8.93 (s, 1H), 8.85-8.21 (m,4H), 8.67 (t, 1H), 8.61 (t, 1H), 8.34 (t, 1H), 7.28 (d, 2H), 7.24-7.19(m, 2H), 7.56 (br, 2H), 5.60 (q, 1H), 4.56-4.50 (m, 1H), 3.50-3.35 (m,2H), 3.32-3.18 (m, 2H), 3.04-3.97 (m, 1H), 2.91-2.87 (m, 1H), 2.84 (d,3H), 2.27-2.18 (m, 1H), 2.10-2.96 (m, 2H). MS (EI) for C₂₇H₂₉N₇O₃: 500(MH⁺).

Example 73

Scheme 29 depicts another strategy for making exemplary compoundsaccording to formula I where W is a substituted phenylene, specificallywhere W possessed a phenolic group and it was desirable to selectivelyalkylate the phenolic oxygen. Compounds (cxvii) were prepared bycoupling phenols with, for example, alkyl bromides, as depicted.

3-Amino-6-(3-{[2-(4-phenylpiperazin-1-yl)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:A mixture of3-amino-6-(3-hydroxyphenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide(0.11 g, 0.27 mmol), 1,2-dibromoethane (4 mL, 46 mmol), and cesiumcarbonate (0.35 g, 1.1 mmol) in DMF (2 mL) was heated at 80° C. for 12h. The reaction mixture was cooled to room temperature, diluted with 1 Naqueous hydrochloric acid solution, and extracted 3× with ethyl acetate,2× with 5% aqueous lithium chloride, and dried over sodium sulfate.Filtration, concentration, and silica gel chromatography gave thecorresponding ether. A mixture of this ether intermediate (0.012 g,0.023 mmol) and N-phenylpiperazine (4.4 mg, 0.027 mmol) was stirred inacetonitrile (5 mL) at room temperature for 3 h. Concentration followedby reverse phase HPLC gave the protected product as a yellow solid. Thissolid was added to 4 N hydrochloric acid in dioxane (5 mL) and themixture was stirred at room temperature for 1 h. Removal of solventunder reduced pressure gave the desired product as a yellow solid (3.2mg, 28% yield). 1H NMR (400 MHz, d₆-DMSO): δ 9.10 (br s, 1H), 8.88 (s,1H), 8.71 (br, 1H), 7.78-7.67 (m, 2H), 7.65 (br s, 1H), 7.42 (t, 1H),7.25 (t, 2H), 7.04-6.98 (m, 3H), 6.85 (t, 1H), 4.56 (br, 2H), 4.24 (br,2H), 3.83 (d, 2H), 3.70-3.63 (m, 4H), 3.48-3.45 (m, 1H), 3.30-3.18 (m,6H), 2.76 (br, 1H), 1.87-1.78 (m, 4H). MS (EI) for C₂₈H₃₅N₇O₂: 502(MH⁺).

Using the same or similar synthetic techniques, substituting with theappropriate reagents such as the respective amines, the followingcompounds of the invention were prepared:

3-Amino-6-{3-[(2-hydroxyethyl)oxy]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.15-9.08 (m, 1H), 8.95-8.92 (m, 1H), 8.85(s, 1H), 8.69 (d, 1H), 7.66 (br s, 1H), 7.69 (d, 1H), 7.63 (s, 1H), 7.36(t, 1H), 6.95 (dd, 1H), 4.22 (br s, 1H), 4.07 (t, 2H), 3.23 (t, 2H),3.05-3.02 (m, 1H), 2.76-2.74 (m, 1H), 1.97-1.88 (m, 2H), 1.76-1.74 (m,2H), 1.26-1.13 (m, 2H), 0.87-0.81 (m, 1H). MS (EI) for C₁₈H₂₃N₅O₃: 358(MH⁺).

3-Amino-6-[3-(methyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.02-8.99 (m, 1H), 8.86 (s, 1H), 8.85 (m,1H), 8.68 (d, 1H), 7.70-7.65 (m, 3H), 7.37 (t, 1H), 6.95 (dd, 1H), 4.24(m, 1H), 3.82 (s, 3H), 3.27-3.19 (m, 2H), 3.07-2.99 (m, 1H), 2.77-2.74(m, 1H), 1.89-1.87 (m, 2H), 1.76-1.72 (m, 2H). MS (EI) for C₁₇H₂₁N₅O₂:328 (MH⁺).

3-Amino-6-[3-(ethyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₆-DMSO): δ 9.03-9.00 (m, 1H), 8.87-8.82 (m, 1H), 8.81(s, 1H), 8.64 (d, 1H), 7.64-7.57 (m, 3H), 7.31 (t, 1H), 6.89 (dd, 1H),4.19-4.17 (m, 1H), 4.06 (q, 2H), 3.22-3.15 (m, 2H), 3.02-2.95 (m, 1H),2.72-2.70 (m, 1H), 1.85-1.83 (m, 2H), 1.71-1.68 (m, 2H), 1.30 (t, 3H).MS (EI) for C₁₈H₂₃N₅O₂: 342 (MH⁺).

3-Amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.63 (s, 1H), 7.64-7.62 (m, 2H), 7.36 (t,1H), 6.98 (d, 1H), 4.40 (br s, 2H), 4.25 (br s, 1H), 3.66-3.63 (m, 2H),3.59-3.51 (m, 9H), 3.50-3.47 (m, 2H), 1.95 (br s, 2H), 1.83 (br, 2H),1.31 (m, 7H). MS (EI) for C₂₂H₃₂N₆O₂: 413 (MH⁺).

3-Amino-6-{3-[(2-morpholin-4-ylethyl)oxy]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.70 (br s, 1H), 7.80 (br s, 1H), 7.71 (d,1H), 7.45 (m, 1H), 7.09 (d, 1H), 4.55 (m, 2H), 4.36 (m, 1H), 4.10-4.06(m, 2H), 3.93 (m, 2H), 3.74-3.71 (m, 2H), 3.67-3.64 (m, 9H), 3.58-3.56(m, 2H), 3.48-3.47 (m, 1H), 2.10-2.04 (m, 2H), 1.89 (m, 2H). MS (EI) forC₂₂H₃₀N₆O₃: 427 (MH⁺).

3-Amino-6-(3-{[2-(ethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide:¹H NMR (400 MHz, d₄-MeOH): δ 8.70 (s, 1H), 7.73-7.70 (m, 2H), 7.44 (t,1H), 7.08 (d, 1H), 4.41-4.34 (m, 2H), 3.75-3.72 (m, 2H), 3.70-3.63 (m,5H), 3.58-3.56 (m, 1H), 3.50 (br s, 2H), 3.37-3.34 (m, 1H), 3.21-3.19(m, 2H), 3.04 (m, 1H), 2.10-2.04 (m, 2H), 1.98-1.92 (m, 2H), 1.38 (t,3H). MS (EI) for C₂₀H₂₈N₆O₂: 385 (MH⁺).

Phenylmethyl4-(2-{[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]oxy}ethyl)piperazine-1-carboxylate:¹H NMR (400 MHz, d₄-MeOH): δ 8.69 (br s, 1H), 7.87 (br s, 1H), 7.70 (m,1H), 7.45 (m, 1H), 7.37-7.31 (m, 4H), 7.10 (d, 1H), 5.16 (s, 2H), 4.56(m, 2H), 4.37-4.28 (m, 4H), 3.74-3.70 (m, 4H), 3.69-3.62 (m, 4H),3.58-3.56 (m, 2H), 3.34 (m, 4H), 3.05 (m, 2H), 2.08 (m, 2H), 1.89 (m,2H). MS (EI) for C₃₀H₃₇N₇O₄: 560 (MH⁺).

3-Amino-N-[(3S)-azepan-3-yl]-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide:¹H NMR (400 MHz, DMSO-d₈): δ 9.59 (m, 2H), 9.25 (bs, 1H), 9.08 (d, 1H),8.96 (s, 1H), 8.78 (m, 1H), 8.48 (d, 1H), 8.32 (m, 1H), 7.92 (m, 1H),7.80 (m, 1H), 7.78 (m, 1H), 7.73 (m, 1H), 7.58 (t, 1H), 7.50 (d, 2H),6.53 (m, 1H), 4.77 (bs, 2H), 4.53 (m, 2H), 4.43 (m, 1H), 3.34 (m, 2H),3.24 (m, 1H), 2.99 (m, 1H), 2.01 (m, 2H), 1.80 (m, 3H), 1.54 (m, 1H); MS(EI) for C₂₈H₃₀N₈O₂ 511.36 (MH⁺).

Assays

Chk1 and Chk2 assays were performed by measuring incorporation of γ-³³PATP into immobilized myelin basic protein (MBP). High binding white 384well plates (Greiner) were coated with MBP (Sigma #M-1891) by incubationof 60 ul/well of 20 μg/ml MBP in Tris-buffered saline (TBS; 50 mM TrispH 8.0, 138 mM NaCl, 2.7 mM KCl) for 24 hours at 4° C. Plates werewashed 3× with 100 μl TBS. Kinase reactions were carried out in a totalvolume of 34 μl in kinase buffer (5 mM Hepes pH 7.6, 15 mM NaCl, 0.01%bovine gamma globulin (Sigma #I-5506), 10 mM MgCl₂, 1 mM DTT, 0.02%TritonX-100). Compound dilutions were performed in DMSO and added toassay wells to a final DMSO concentration of 1%. Each data point wasmeasured in duplicate, and at least two duplicate assays were performedfor each individual compound determination. Chk1 and Chk2 enzymes(Upstate Biotechnology) were added to final concentrations of 10 nM(Chk1) or 20 nM (Chk2). A mixture of unlabeled ATP and γ-³³P ATP wasadded to start the reaction (2×10⁶ cpm of γ-³³P ATP per well (3000Ci/mmole) and either 10 μM or 30 μM unlabeled ATP (for Chk1 and Chk2assays respectively). The reaction was carried out for 1 hour at roomtemperature with shaking. Plates were washed 7× with TBS, followed bythe addition of 50 μl/well scintillation fluid (Wallac). Plates wereread using a Wallac Trilux counter. This is only one format of suchassays, various other formats are possible, as known to those skilled inthe art.

The above assay procedure can be used to determine the IC₅₀ forinhibition and/or the inhibition constant K_(i). The IC₅₀ is defined asthe concentration of compound required to reduce the enzyme activity by50% under the conditions of the assay. Exemplary compositions haveIC₅₀'s of, for example, less than about 100 μM, less than about 10 μM,less than about 1 μM, and further for example having IC₅₀'s of less thanabout 100 nM, and still further, for example, less than about 10 nM. TheK_(i) for a compound may be determined from the IC₅₀ based on threeassumptions. First, only one compound molecule binds to the enzyme andthere is no cooperativity. Second, the concentrations of active enzymeand the compound tested are known (i.e., there are no significantamounts of impurities or inactive forms in the preparations). Third, theenzymatic rate of the enzyme-inhibitor complex is zero. The rate (i.e.,compound concentration) data are fitted to the equation:

$V = {V_{\max}{E_{0}\left\lbrack {I - \frac{\left( {E_{0} + I_{0} + K_{d}} \right) - {\sqrt{\left( {E_{0} + I_{0} + K_{d}} \right)^{2} - {4E_{0}}}I_{0}}}{2E_{0}}} \right\rbrack}}$

Where V is the observed rate, V_(max), is the rate of the free enzyme,I₀ is the inhibitor concentration, E₀ is the enzyme concentration, andK_(d) is the dissociation constant of the enzyme-inhibitor complex.

Kinase Specificity Assays:

Kinase activity and compound inhibition are investigated using one ormore of the three assay formats described below. The ATP concentrationsfor each assay are selected to be close to the Michaelis-Menten constant(K_(M)) for each individual kinase. Dose-response experiments areperformed at 10 different inhibitor concentrations in a 384-well plateformat. The data are fitted to the following four-parameter equation:Y=Min+(Max−Min)/(1+(X/IC₅₀)^H)where Y is the observed signal, X is the inhibitor concentration, Min isthe background signal in the absence of enzyme (0% enzyme activity), Maxis the signal in the absence of inhibitor (100% enzyme activity), IC₅₀is the inhibitor concentration at 50% enzyme inhibition and H representsthe empirical Hill's slope to measure the cooperativity. Typically H isclose to unity.³³P Phosphoryl Transfer Assay:

Greiner 384-well white, clear bottom, high binding plates are coatedwith 2 μg/well of protein or peptide substrate in a 50 μL volumeovernight at ambient temperature. The coating buffer typically contains40 μg/mL substrate, 22.5 mM Na₂CO₃, 27.5 mM NaHCO₃, 150 mM NaCl and 3 mMNaN₃. The coating solution is aspirated and the plates are washed oncewith 50 μL of assay buffer and padded dry. Subsequently compounds andenzymes are mixed with γ³³P-ATP (3.3 μCi/nmol) in a total volume of 20uL in suitable assay buffers. The mixture is incubated at ambienttemperature for 1.5-2.5 hrs and terminated by aspiration using aMolecular Devices EMBLA 96-head plate washer. The plates aresubsequently washed 6-12 times with PBST or TBS buffer. Scintillationfluid (50 μl/well) is then added, the plates are sealed and activityassessed by liquid scintillation spectrometry using a Perkin ElmerMicroBeta TriLux.

Luciferase-Coupled Chemiluminescent Assay (LCCA)

In the LCCA assays, kinase activity is measured as the percent ATPconsumed following the kinase reaction usingluciferase-luciferin-coupled chemiluminescence. Greiner 384-well white,clear bottom, medium binding plates are used for LCCA. Briefly, thekinase reaction is initiated by mixing compounds, ATP and kinase in a 20uL volume. The mixture is incubated at ambient temperature for 2-4 hrs.At the end of the kinase reaction, a 20 uL luciferase-luciferin mix isadded and the chemiluminescent signal is read using a Wallac Victor²reader. The luciferase-luciferin mix consists of 50 mM HEPES, pH 7.8,8.5 ug/mL oxalic acid (pH 7.8), 5 (or 50) mM DTT, 0.4% Triton X-100,0.25 mg/mL coenzyme A, 63 uM AMP, 28 ug/mL luciferin and 40,000 units oflight/mL luciferase. For the LCCA assays, total ATP consumption has beenstandardized to 25-45% and the IC₅₀ values correlates well with thosedetermined by radiometric assays.

AlphaScreen

AlphaScreen technology is a proximity assay which utilizes the increasein fluorescent signal when donor and acceptor beads are close inproximity. Biotinylated poly(Glu,Tyr) 4:1 is used as the kinasesubstrate, in conjunction with streptavidin-coated donor beads andanti-phosphortyrosine antibody PY100-coated acceptor beads. Uponphosphorylation, the peptide substrate can bind to both donor andacceptor beads giving rise to an increase in fluorescence. Compounds,ATP, biotinylated poly(Glu, Tyr) and kinases are mixed in a volume of 20uL for 1 hr at ambient temperature using Greiner 384-well white clearbottom medium binding plates. Following incubation a 10 uL solutioncontaining 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mMNaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well.After 2-16 hr incubation of the beads, plates are read in a Perkin ElmerAlphaQuest reader. The IC₅₀ values correlates well with those ofradiometric assays.

In order to assess the ability of the compound to abrogate the G2checkpoint in cells (via Chk1 inhibition), a mitotic index assay can beperformed. Mitotic index was determined by measuring accumulation ofcells in mitosis in the presence of a DNA damaging agent (for example,Adriamycin; Adr). Nocodozole (Noc) was used to induce mitotic arrest. Inthe presence of Noc, cells accumulate in mitosis and are detected usingan M-phase specific antibody. In the presence of Adr and Noc, cellsundergo G2 arrest and do not proceed to M-phase. Addition of Chk1inhibitors causes the G2 checkpoint to be bypassed, and M-phase cellsare detected. HT-29 cells were cultured by 1:20 passaging in DMEM+10%fetal bovine serum (DMEM/FBS) at 37° C. and 5% CO₂. Prior to the assay,cells were plated at 6500 cells/well in 100 μl DMEM/FBS in black/clearbottom 96 well plates (BD Biocoat). After growing for 24 hours at 37°C./5% CO₂, Adr was added to a final concentration of 250 nM and cellswere grown for a further 18-20 hrs. Medium was then aspirated from theplates and 70 μl of 0.7 μM Noc added in DMEM/FBS containing 0.55% v/vDMSO. Compounds were diluted in DMEM/FBS containing 0.55% v/v DMSO, and30 μl of compound solution added to the assay plates. Control wells withNoc, compound/Noc and Noc/Adr alone were also set up. Cells were grownfor a further 18-20 hrs and visually inspected before fixing withformaldehyde. The percentage of mitotic cells was determined byimmunofluoresence using a M-phase specific anti-phosphohistoneH3 rabbitpolyclonal antibody and a goat anti-rabbit secondary antibody conjugatedto Alexa Fluor 488 dye. Cell nuclei were also stained using Hoechst dye.Staining and fluorescence detection was performed using a CellomicsArrayscan instrument, using the manufacturer's mitotic index assay kit.This is only one format of such assays, various other formats arepossible, as known to those skilled in the art.

Structure Activity Relationships

Table 11 shows structure activity relationship data for selectedcompounds of the invention with respect to Chk1 only. Inhibition isindicated as IC₅₀ with following key: A=IC₅₀ less than 50 nM, B=IC₅₀greater than 50 nM but less than or equal to 1000 nM, C=IC₅₀ greaterthan 1000 nM but less than 10,000 nM, and D=IC₅₀ of 10,000 nM orgreater.

TABLE 11 # Name Chk1 IC₅₀ 13-amino-6-phenyl-N-(2-phenylethyl)pyrazine-2-carboxamide D 23-amino-6-phenyl-N-(phenylmethyl)pyrazine-2-carboxamide D 33-amino-6-(3-chlorophenyl)pyrazine-2-carboxamide D 43-amino-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-6-phenylpyrazine-2- Dcarboxamide 53-amino-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-6-phenylpyrazine-2- Dcarboxamide 63-amino-N-(2,3-dihydro-1H-inden-2-yl)-6-phenylpyrazine-2-carboxamide D 73-amino-6-(2-chlorophenyl)pyrazine-2-carboxamide D 83-amino-N-cyclopentyl-6-phenylpyrazine-2-carboxamide D 93-amino-N,N-dimethyl-6-phenylpyrazine-2-carboxamide C 103-amino-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide C 115-phenyl-3-(pyrrolidin-1-ylcarbonyl)pyrazin-2-amine D 123-amino-N-(cyclopropylmethyl)-6-phenylpyrazine-2-carboxamide D 133-amino-6-phenyl-N-(tetrahydrofuran-2-ylmethyl)pyrazine-2-carboxamide D14 3-amino-N-cyclohexyl-6-phenylpyrazine-2-carboxamide D 156-phenyl-N-propyl-3-(propylamino)pyrazine-2-carboxamide D 163-amino-6-(2-methylphenyl)pyrazine-2-carboxamide D 173-amino-6-[2-(methyloxy)phenyl]pyrazine-2-carboxamide D 183-amino-6-(2,4-difluorophenyl)pyrazine-2-carboxamide D 193-amino-6-(3-fluorophenyl)pyrazine-2-carboxamide D 203-amino-N-cyclopropyl-6-phenylpyrazine-2-carboxamide D 213-amino-6-(3,4-difluorophenyl)pyrazine-2-carboxamide D 223-amino-6-(4-fluorophenyl)-N-methylpyrazine-2-carboxamide C 233-amino-6-[4-(ethyloxy)phenyl]pyrazine-2-carboxamide C 243-amino-6-[3-(ethyloxy)phenyl]pyrazine-2-carboxamide C 253-amino-6-(1,3-benzodioxol-5-yl)pyrazine-2-carboxamide D 263-amino-6-naphthalen-1-ylpyrazine-2-carboxamide D 273-amino-6-naphthalen-2-ylpyrazine-2-carboxamide D 283-amino-6-{3-[(trifluoromethyl)oxy]phenyl}pyrazine-2-carboxamide C 293-amino-6-[3-(aminocarbonyl)phenyl]pyrazine-2-carboxamide C 306-[3-(acetylamino)phenyl]-3-aminopyrazine-2-carboxamide C 313-amino-6-biphenyl-4-ylpyrazine-2-carboxamide D 323-amino-6-[4-(dimethylamino)phenyl]pyrazine-2-carboxamide C 333-amino-6-(3-methylphenyl)pyrazine-2-carboxamide C 34 methyl3-[5-amino-6-(aminocarbonyl)pyrazin-2-yl]benzoate C 353-amino-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide B 363-amino-6-(3-hydroxyphenyl)pyrazine-2-carboxamide B 373-amino-6-(1-benzofuran-2-yl)pyrazine-2-carboxamide D 383-(methylamino)-6-phenylpyrazine-2-carboxamide D 396-phenyl-3-[(phenylmethyl)amino]pyrazine-2-carboxamide D 406-phenyl-3-(propylamino)pyrazine-2-carboxamide D 413-amino-6-biphenyl-3-ylpyrazine-2-carboxamide B 423-[5-amino-6-(aminocarbonyl)pyrazin-2-yl]benzoic acid D 433-amino-6-{4-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide D 443-amino-N-methyl-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide C45 3-amino-6-(3-hydroxyphenyl)-N-methylpyrazine-2-carboxamide B 463-amino-N-[2-(methyloxy)ethyl]-6-phenylpyrazine-2-carboxamide C 47N-[2-(acetylamino)ethyl]-3-amino-6-phenylpyrazine-2-carboxamide D 483-amino-6-phenylpyrazine-2-carbohydrazide C 493-amino-N-hydroxy-6-phenylpyrazine-2-carboxamide C 503-amino-6-[3-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide C 513-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide B 523-amino-6-[4-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide C 533-amino-N-methyl-6-(3-methylphenyl)pyrazine-2-carboxamide B 543-amino-N-methyl-6-[4-(methyloxy)phenyl]pyrazine-2-carboxamide C 553-amino-6-biphenyl-3-yl-N-methylpyrazine-2-carboxamide B 566-[3-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide B 573-amino-6-[3-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide B 583-amino-6-[4-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide C 593-amino-N-methyl-6-{3-[(1E)-N-methylethanimidoyl]phenyl}pyrazine-2- Ccarboxamide 603-amino-N-methyl-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide C 613-amino-6-(4-fluoro-3-methylphenyl)-N-methylpyrazine-2-carboxamide B 623-amino-N-methyl-6-pyridin-3-ylpyrazine-2-carboxamide C 636-[4-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide C 643-amino-N-methyl-6-{3-[(methylamino)carbonyl]phenyl}pyrazine-2- Ccarboxamide 65 6-(3-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamideC 66 3-amino-N-methyl-6-(5-pyridin-3-yl-1,2,4-oxadiazol-3-yl)pyrazine-2-D carboxamide 673-amino-6-(5-cyclopentyl-1,2,4-oxadiazol-3-yl)-N-methylpyrazine-2- Dcarboxamide 683-amino-6-(5-cyclohexyl-1,2,4-oxadiazol-3-yl)-N-methylpyrazine-2- Dcarboxamide 693-amino-N-methyl-6-(5-phenyl-1,2,4-oxadiazol-3-yl)pyrazine-2- Dcarboxamide 703-amino-N-methyl-6-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]pyrazine-2- Dcarboxamide 713-amino-N-methyl-6-(5-methyl-1,2,4-oxadiazol-3-yl)pyrazine-2- Ccarboxamide 723-amino-N-methyl-6-[5-(2-phenylethyl)-1,2,4-oxadiazol-3-yl]pyrazine-2- Dcarboxamide 733-amino-N-methyl-6-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl)pyrazine-2- Dcarboxamide 743-amino-6-[5-(1,1-dimethylethyl)-1,2,4-oxadiazol-3-yl]-N-methylpyrazine-2-D carboxamide 753-amino-6-(5-furan-2-yl-1,2,4-oxadiazol-3-yl)-N-methylpyrazine-2- Dcarboxamide 763-amino-6-[4-(dimethylamino)phenyl]-N-methylpyrazine-2-carboxamide C 773-amino-N-methyl-6-{4-[(methylsulfonyl)amino]phenyl}pyrazine-2- Ccarboxamide 783-amino-6-(3,5-dimethylphenyl)-N-methylpyrazine-2-carboxamide C 796-(4-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamide C 803-amino-6-[3,4-bis(methyloxy)phenyl]-N-methylpyrazine-2-carboxamide C 813-amino-N-methyl-6-{3-[(phenylcarbonyl)amino]phenyl}pyrazine-2- Bcarboxamide 823-amino-N-methyl-6-{3-[(methylsulfonyl)amino]phenyl}pyrazine-2- Ccarboxamide 833-amino-N-methyl-6-[3-(1H-tetrazol-5-yl)phenyl]pyrazine-2-carboxamide C843-amino-N-methyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-B carboxamide 853-amino-6-[3-(aminocarbonyl)phenyl]-N-methylpyrazine-2-carboxamide C 863-amino-6-{3-[(dimethylamino)carbonyl]phenyl}-N-methylpyrazine-2- Ccarboxamide 873-amino-N-methyl-6-[4-(methylsulfonyl)phenyl]pyrazine-2-carboxamide C 883-amino-6-(3-aminophenyl)-N-ethylpyrazine-2-carboxamide C 893-amino-6-[3-({[(4-fluorophenyl)amino]carbonyl}amino)phenyl]-N- Bmethylpyrazine-2-carboxamide 90 3-amino-N-methyl-6-{3-[({[4- B(methyloxy)phenyl]amino}carbonyl)amino]phenyl}pyrazine-2-carboxamide 916,6′-[(oxomethanediyl)bis(iminobenzene-3,1-diyl)]bis(3-amino-N- Amethylpyrazine-2-carboxamide) 923-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid D 933-amino-N-methyl-6-{3-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazine-C 2-carboxamide 943-amino-N-methyl-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-B carboxamide 95 3-amino-N-methyl-6-{3-[({[4- B(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 963-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- Cmethylpyrazine-2-carboxamide 973-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 983-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 99 3-amino-N-methyl-6-(3- C{[methyl(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1003-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 101 3-amino-N-methyl-6-[3-({[(4- Bmethylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1023-amino-N-methyl-6-{3-[({[4- B(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 1033-amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 1043-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N- Bmethylpyrazine-2-carboxamide 105 3-amino-N-methyl-6-[3-({[3- B(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 1063-amino-N-methyl-6-[3-({[4- B(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 1073-amino-N-methyl-6-{3-[({[3- B(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide108 3-amino-N-methyl-6-{3-[({(1R)-1-[4- C(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 1093-amino-N-methyl-6-{3-[({[2- B(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 1103-amino-6-[3-({[(3-fluorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 1113-amino-6-(3-{[(4-chlorophenyl)carbonyl]amino}phenyl)-N-methylpyrazine-B 2-carboxamide 1123-amino-6-[3-({[1-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N- Cmethylpyrazine-2-carboxamide 1133-amino-6-{3-[({[2,3-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-B N-methylpyrazine-2-carboxamide 1143-amino-6-(3-{[bis(phenylmethyl)amino]carbonyl}phenyl)-N- Cmethylpyrazine-2-carboxamide 1153-amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-B N-methylpyrazine-2-carboxamide 1163-amino-6-(3-{[ethyl(pyridin-4-ylmethyl)amino]carbonyl}phenyl)-N- Cmethylpyrazine-2-carboxamide 1173-amino-N-methyl-6-(3-{[4-(phenylmethyl)piperazin-1- Cyl]carbonyl}phenyl)pyrazine-2-carboxamide 1183-amino-N-methyl-6-[3-({[1-(phenylmethyl)piperidin-4- Byl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1193-amino-N-methyl-6-(3-{[(4-methylphenyl)carbonyl]amino}phenyl)pyrazine-B 2-carboxamide 120 3-amino-N-methyl-6-[3-({[(5-methylpyrazin-2- Cyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1213-amino-N-methyl-6-(3-{[(pyridin-2- Bylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1223-amino-N-methyl-6-(3-{[(pyridin-3- Bylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1233-amino-N-methyl-6-(3-{[(pyridin-4- Bylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1243-amino-6-{3-[(furan-2-ylcarbonyl)amino]phenyl}-N-methylpyrazine-2- Bcarboxamide 1253-amino-6-[3-({[(3-chlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 1263-amino-6-(3-{[(cyclohexylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 1273-amino-N-methyl-6-(3-{[(2-phenylpropyl)amino]carbonyl}phenyl)pyrazine-B 2-carboxamide 1283-amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 1293-amino-6-[3-({[2-(2-chlorophenyl)ethyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 130 3-amino-N-methyl-6-{3-[({2-[2- B(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 1313-amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 132 3-amino-N-methyl-6-[3-({[2-(2- Bthienyl)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1333-amino-6-{3-[(cyclohexylamino)carbonyl]phenyl}-N-methylpyrazine-2- Ccarboxamide 134 1,1-dimethylethyl4-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- Byl}phenyl)carbonyl]amino}methyl)piperidine-1-carboxylate 1353-amino-N-methyl-6-(3-{[(piperidin-4- Bylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1363-amino-N-methyl-6-[3-(5-phenyl-1,2,4-oxadiazol-3-yl)phenyl]pyrazine-2-C carboxamide 1373-amino-N-methyl-6-{3-[5-(phenylmethyl)-1,2,4-oxadiazol-3- Cyl]phenyl}pyrazine-2-carboxamide 1383-amino-N-methyl-6-{3-[5-(2-phenylethyl)-1,2,4-oxadiazol-3- Cyl]phenyl}pyrazine-2-carboxamide 1393-amino-6-(3-{[(1,1-dimethylethyl)amino]carbonyl}phenyl)-N- Cmethylpyrazine-2-carboxamide 1403-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Byl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1413-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1- Cyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 1423-amino-N-methyl-6-{3-[(phenylamino)carbonyl]phenyl}pyrazine-2- Ccarboxamide 1433-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-N- Cmethylpyrazine-2-carboxamide 144 3-amino-N-methyl-6-[3-({[(1R)-1- Cphenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1453-amino-N-methyl-6-[3-({[(1S)-1- Bphenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1463-amino-N-methyl-6-[3-({[(1R)-1- Cphenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1473-amino-N-methyl-6-[3-({[(1S)-1- Cphenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1483-amino-N-methyl-6-[3-({[(1R,2S)-2- Bphenylcyclopropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 149phenylmethyl 4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoate D1503-amino-N-methyl-6-(4-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-C carboxamide 1513-amino-N-methyl-6-(4-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-B carboxamide 1523-amino-6-[4-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 153 3-amino-N-methyl-6-[4-({[(4- Bmethylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1543-amino-6-(4-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 1553-amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-B carboxamide 156 3-amino-N-methyl-6-[3-({[3- B(phenyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 1573-amino-6-{3-[(diphenylacetyl)amino]phenyl}-N-methylpyrazine-2- Bcarboxamide 1583-amino-N-methyl-6-{3-[(phenylacetyl)amino]phenyl}pyrazine-2- Bcarboxamide 1593-amino-N-methyl-6-{3-[(3-phenylpropanoyl)amino]phenyl}pyrazine-2- Bcarboxamide 1603-amino-N-methyl-6-(3-{[(1R)-1,2,3,4-tetrahydronaphthalen-1- Cylamino]carbonyl}phenyl)pyrazine-2-carboxamide 1613-amino-N-methyl-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1- Bylamino]carbonyl}phenyl)pyrazine-2-carboxamide 1623-amino-N-methyl-6-{3-[({[3,4,5- Btris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 163 3-amino-N-methyl-6-{3-[({(1R,2R)-2- C[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 164 3-amino-N-methyl-6-{3-[({(1S,2S)-2- B[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 165 3-amino-6-(3-cyanophenyl)-N-methylpyrazine-2-carboxamideC 1663-amino-6-{3-[(cyclopentylcarbonyl)amino]phenyl}-N-methylpyrazine-2- Bcarboxamide 1673-amino-6-(3-{[(4-cyanophenyl)carbonyl]amino}phenyl)-N-methylpyrazine- B2-carboxamide 168 3-amino-N-methyl-6-[3- B({[(phenylmethyl)amino]carbonyl}amino)phenyl]pyrazine-2-carboxamide 1693-amino-N-methyl-6-(3-{[(naphthalen-2- Bylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1703-amino-N-methyl-6-(3-{[(tetrahydrofuran-2- Cylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 1713-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 172 3-amino-6-{3-[({[3-fluoro-5- B(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 1733-amino-6-{3-[({2-[3,5-bis(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}-C N-methylpyrazine-2-carboxamide 1743-amino-N-methyl-6-{3-[(2-phenylethyl)oxy]phenyl}pyrazine-2-carboxamideB 175 3-amino-N-methyl-6-(3-{[2-(4-methylpiperidin-1- Cyl)ethyl]oxy}phenyl)pyrazine-2-carboxamide 1763-amino-6-[3-({2-[4-(2-hydroxyethyl)piperidin-1-yl]ethyl}oxy)phenyl]-N-C methylpyrazine-2-carboxamide 1773-amino-6-(3-{[2-(3-hydroxypyrrolidin-1-yl)ethyl]oxy}phenyl)-N- Cmethylpyrazine-2-carboxamide 1783-amino-6-[3-({2-[ethyl(phenylmethyl)amino]ethyl}oxy)phenyl]-N- Bmethylpyrazine-2-carboxamide 1793-amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-methylpyrazine-2- Bcarboxamide 1803-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N- Amethylpyrazine-2-carboxamide 1813-amino-N-methyl-6-(3-{[2-(4-phenylpiperazin-1- Byl)ethyl]oxy}phenyl)pyrazine-2-carboxamide 1823-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N- Amethylpyrazine-2-carboxamide 183 3-amino-N-methyl-6-[3-({2- B[methyl(phenylmethyl)amino]ethyl}oxy)phenyl]pyrazine-2-carboxamide 1843-amino-N-methyl-6-{3-[({[4- B(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide185 3-amino-N-methyl-6-{3-[(2-morpholin-4-ylethyl)oxy]phenyl}pyrazine-2-C carboxamide 1863-amino-6-[3-({2-[(cyclopropylmethyl)(propyl)amino]ethyl}oxy)phenyl]-N-B methylpyrazine-2-carboxamide 1873-amino-N-methyl-6-[3-({2-[4-(phenylmethyl)piperidin-1- Byl]ethyl}oxy)phenyl]pyrazine-2-carboxamide 1883-amino-N-methyl-6-{3-[(2-piperidin-1-ylethyl)oxy]phenyl}pyrazine-2- Bcarboxamide 189 3-amino-N-methyl-6-{3-[({[3- B(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide190 3-amino-6-(3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}phenyl)-N- Bmethylpyrazine-2-carboxamide 1913-amino-N-methyl-6-{3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}pyrazine-2- Bcarboxamide 192 3-amino-N-methyl-6-(3-{[2-(4-methylpiperazin-1- Byl)ethyl]oxy}phenyl)pyrazine-2-carboxamide 1933-amino-6-[3-({2-[4-(2-hydroxyethyl)piperazin-1-yl]ethyl}oxy)phenyl]-N-B methylpyrazine-2-carboxamide 1943-amino-6-(3-{[2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl]oxy}phenyl)-N- Bmethylpyrazine-2-carboxamide 195 ethyl4-{2-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- Cyl}phenyl)oxy]ethyl}piperazine-1-carboxylate 1963-amino-N-methyl-6-[3-({[(3S)-1-(phenylmethyl)pyrrolidin-3- Byl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1973-amino-N-methyl-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3- Byl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1983-amino-N-methyl-6-[3-({[2- B(phenyloxy)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1993-amino-N-methyl-6-{3-[({2-[4-(phenylmethyl)piperazine-1- Byl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2003-amino-N-methyl-6-{3-[({[1-(phenylmethyl)piperidin-4- Dyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2013-amino-6-(3-{[(furan-3-ylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 2023-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2- Bylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2033-amino-6-(3-{[(furan-2-ylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 2043-amino-N-methyl-6-{3-[({[4-(phenylmethyl)morpholin-2- Byl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2053-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6- Aylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2063-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6- Aylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2073-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5- Bylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 2083-amino-6-[3-({[(6-fluoro-4H-1,3-benzodioxin-8- Byl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2093-amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N- Amethylpyrazine-2-carboxamide 2103-amino-6-(3-{[(3,4-dichlorophenyl)acetyl]amino}phenyl)-N- Bmethylpyrazine-2-carboxamide 211 3-amino-N-methyl-6-[3-({[4- B(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide 2123-amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2133-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-B N-methylpyrazine-2-carboxamide 2143-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2153-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N- Cmethylpyrazine-2-carboxamide 216 3-amino-N-methyl-6-{3-[({[4- A(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide2173-amino-N-methyl-6-(3-{[(2-methylpropyl)amino]carbonyl}phenyl)pyrazine-C 2-carboxamide 218 3-amino-N-methyl-6-(3-{[({3- C[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2193-amino-6-(3-{[(cyclopropylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 2203-amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-methylpyrazine-2- Ccarboxamide 2213-amino-N-methyl-6-(3-{[(4-methylphenyl)amino]carbonyl}phenyl)pyrazine-C 2-carboxamide 222 3-amino-N-methyl-6-[3-({[4- B(methyloxy)phenyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2233-amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 2243-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 225 3-amino-N-methyl-6-(3-{[(1-methyl-1- Cphenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2263-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 227 3-amino-N-methyl-6-(3-{[({4- B[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 228 3-amino-6-{3-[({[4-fluoro-3- B(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 229 3-amino-6-{3-[({[4-chloro-3- B(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2303-amino-6-[3-({[(4-aminophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2313-amino-6-[3-({[(2-aminophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2323-amino-6-[3-({[(3-aminophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2333-amino-N-methyl-6-pyrimidin-5-ylpyrazine-2-carboxamide D 2343-amino-N-methyl-6-[3-(methylsulfonyl)phenyl]pyrazine-2-carboxamide C2353-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2- Bcarboxamide 2363-amino-6-(4-hydroxyphenyl)-N-methylpyrazine-2-carboxamide B 2373-amino-6-{3-[({[4-(aminosulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-B N-methylpyrazine-2-carboxamide 2383-amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-B N-methylpyrazine-2-carboxamide 2393-amino-6-[3-({[(3-bromophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2403-amino-6-(4-chloro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 241 methyl3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate D 242methyl 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate C 2433-amino-6-[3-({[(2,3-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 244 3-amino-6-{3-[({[4-hydroxy-3- B(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2453-amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-B N-methylpyrazine-2-carboxamide 2463-amino-6-{3-[({[2-(ethyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N- Bmethylpyrazine-2-carboxamide 247 3-amino-6-{3-[({[2-chloro-6- B(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2483-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2493-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-C N-methylpyrazine-2-carboxamide 2503-amino-6-[3-({[(2-chloro-6-methylphenyl)methyl]amino}carbonyl)phenyl]-B N-methylpyrazine-2-carboxamide 251 3-amino-N-methyl-6-[3-({[(2,4,5- Btrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2523-amino-6-(3-{[(2,2-dimethylpropyl)amino]carbonyl}phenyl)-N- Cmethylpyrazine-2-carboxamide 2533-amino-6-(3-{[(cyclopentylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 2543-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-B N-methylpyrazine-2-carboxamide 255 3-amino-N-methyl-6-{3-[({[4- B(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2563-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 2573-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 258 3-amino-N-methyl-6-{3-[({[2,4,6- Btris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 259 3-amino-N-methyl-6-[3-({[(3- Bmethylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2603-amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 2613-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 262 3-amino-6-{3-[({[3,5- Bbis(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 2633-amino-6-(3-{[(2,2-diphenylethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 2643-amino-N-methyl-6-(3-thienyl)pyrazine-2-carboxamide B 2653-amino-N-methyl-6-(3-{[(phenylmethyl)amino]sulfonyl}phenyl)pyrazine-2-C carboxamide 2665,5′-diamino-N,N′-dimethyl-2,2′-bipyrazine-6,6′-dicarboxamide D 2673-amino-6-(1H-indol-5-yl)-N-methylpyrazine-2-carboxamide B 2683-amino-N-methyl-6-(2-thienyl)pyrazine-2-carboxamide B 2693-amino-N-methyl-6-pyridin-4-ylpyrazine-2-carboxamide C 2703-amino-N-cyclopropyl-6-(3- C{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 2713-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-D cyclopropylpyrazine-2-carboxamide 2723-amino-N-ethyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2- Ccarboxamide 2733-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-C ethylpyrazine-2-carboxamide 2743-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2753-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A methylpyrazine-2-carboxamide 2763-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2773-amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 2783-amino-6-{3-[(cyclopropylamino)carbonyl]phenyl}-N-methylpyrazine-2- Ccarboxamide 2793-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2803-amino-6-[3-({[(4′-fluorobiphenyl-2-yl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 281 3-amino-N-methyl-6-[3-({[(2,3,4- Btrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2823-amino-6-[3-({[(3-chloro-2,6- Bdifluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 283 3-amino-6-[3-({[(3-chloro-2,6- Bdifluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2843-amino-6-{3-[(9H-fluoren-9-ylamino)carbonyl]phenyl}-N-methylpyrazine-2-D carboxamide 285 3-amino-N-methyl-6-[3-({[(2- Bmethylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2863-amino-6-[3-({[(3,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2873-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 2883-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2893-amino-6-[3-({[(2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 2903-amino-N-methyl-6-{3-[({[4-(4-methylpiperazin-1- Cyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 2913-amino-6-(4-fluoro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 292 3-amino-N-methyl-6-[3-({[(2,4,6- Btrichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 2933-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-B N-methylpyrazine-2-carboxamide 2943-amino-6-{3-[({[2,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-B N-methylpyrazine-2-carboxamide 2953-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 296 3-amino-6-[3-({[(2-chloro-6-fluoro-3-B methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 297 3-amino-6-[3-({[(2-chloro-3,6- Bdifluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 298 3-amino-6-[3-({[(2,3-difluoro-4- Bmethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 2993-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 3003-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 301 3-amino-6-[3-({[(6-chloro-2-fluoro-3-B methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3023-amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N- Amethylpyrazine-2-carboxamide 3033-amino-6-[3-({[(3-chloro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-B N-methylpyrazine-2-carboxamide 3043-amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3053-amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 306 3-amino-N-methyl-6-[3-({[(2,3,6- Btrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3073-amino-N-methyl-6-[3-({[(2,3,6- Btrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3083-amino-N-methyl-6-(3-{[(phenylcarbonyl)amino]methyl}phenyl)pyrazine-2-B carboxamide 3093-amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3103-amino-6-[3-({[(2,5-difluorophenyl)carbonyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 311 3-amino-N-methyl-6-(3-{[(naphthalen-2-B ylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3123-amino-N-methyl-6-(3-{[(phenylmethyl)thio]methyl}phenyl)pyrazine-2- Bcarboxamide 3133-amino-N-methyl-6-(3-{[(phenylmethyl)sulfonyl]methyl}phenyl)pyrazine-2-B carboxamide 3143-amino-N-methyl-6-(3-{[(phenylmethyl)oxy]methyl}phenyl)pyrazine-2- Bcarboxamide 3153-amino-N-methyl-6-(3-{[(phenylmethyl)amino]methyl}phenyl)pyrazine-2- Bcarboxamide 316 3-amino-N-methyl-6-[3-({[(3,4,5- Btrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3179H-fluoren-9-ylmethyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- Cyl}phenyl)carbamate 318 phenylmethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- B yl}phenyl)carbamate319 ethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate B 3203-amino-6-[3-({[(3,4-dichlorophenyl)carbonyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 321 1,1-dimethylethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- C yl}phenyl)carbamate322 (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl (3-{5-amino-6- D[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate 3233-amino-6-[3-({[(4-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3243-amino-N-methyl-6-(3-{[({4-[(2-morpholin-4- Bylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide325 3-amino-N-methyl-6-{3-[({[2- B(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide326 3-amino-6-[3-({[(3-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3273-amino-6-[3-({[(2-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3283-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2- Acarboxamide 3293-amino-N-(2-hydroxyethyl)-6-(3-methylphenyl)pyrazine-2-carboxamide C3303-amino-N-methyl-6-(3-{[(phenylacetyl)amino]methyl}phenyl)pyrazine-2- Bcarboxamide 3313-amino-6-[3-({[(4-chlorophenyl)acetyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3323-amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N- Amethylpyrazine-2-carboxamide 333 3-amino-6-{3-[({[2-chloro-5- B(trifluoromethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 334N-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)methyl]-1H-B indole-2-carboxamide 3353-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-B methylpyrazine-2-carboxamide 3363-amino-6-(3-{[(1H-indol-3-ylacetyl)amino]methyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 3373-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3383-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3393-amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N- Amethylpyrazine-2-carboxamide 3403-amino-6-[3-({[(3-iodophenyl)methyl]amino}carbonyl)phenyl]-N- Amethylpyrazine-2-carboxamide 3413-amino-N-methyl-6-[3-({[(2-morpholin-4- Bylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3423-amino-N-methyl-6-(3-{[({3-[(2-morpholin-4- Bylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide343 3-amino-N-methyl-6-[3-({[(4-morpholin-4- Bylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3443-amino-N-methyl-6-[3-({[(3-morpholin-4- Cylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3453-amino-N-methyl-6-{3-[({[4-(1- Bmethylethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide346 3-amino-N-methyl-6-(3-{[({[4-(1- Bmethylethyl)phenyl]oxy}acetyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3473-amino-6-{3-[({[(4-aminophenyl)thio]acetyl}amino)methyl]phenyl}-N- Bmethylpyrazine-2-carboxamide 348 3-amino-N-methyl-6-(4-(methyloxy)-3- B{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3493-amino-N-methyl-6-(5-{[(phenylmethyl)amino]carbonyl}pyridin-3- Byl)pyrazine-2-carboxamide 3503-amino-6-[3-({[(4-iodophenyl)carbonyl]amino}methyl)phenyl]-N- Amethylpyrazine-2-carboxamide 351 3-amino-N-methyl-6-[3-({[(4- Bpentylphenyl)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide 3523-amino-6-(3-{[(1,3-benzodioxol-5-ylcarbonyl)amino]methyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 353 3-amino-6-{3-[({[(4-(1,1- Bdimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3543-amino-N-methyl-6-(3-{[({1-[5-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-B yl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3553-amino-N-methyl-6-[3-({[(2-piperidin-1- Bylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3563-amino-N-methyl-6-{3-[({[2- A(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide357 1,1-dimethylethyl(3R)-3-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- Cyl}phenyl)carbonyl]amino}pyrrolidine-1-carboxylate 3583-amino-N-methyl-6-(3-{[(3R)-pyrrolidin-3- Cylamino]carbonyl}phenyl)pyrazine-2-carboxamide 3593-{[(4-chlorophenyl)methyl]amino}-6-{3-[({(3R)-1-[(4- Bchlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3603-amino-6-{3-[({(3R)-1-[(2,4-dichlorophenyl)methyl]pyrrolidin-3- Byl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 361N-methyl-3-({[3-(methyloxy)phenyl]methyl}amino)-6-(3-{[((3R)-1-{[3- B(methyloxy)phenyl]methyl}pyrrolidin-3-yl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3623-amino-6-{3-[({(3R)-1-[(2,6-dichlorophenyl)methyl]pyrrolidin-3- Byl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 363N-methyl-3-[(phenylmethyl)amino]-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-B 3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3641,1-dimethylethyl 3-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- Byl}phenyl)carbonyl]amino}methyl)pyrrolidine-1-carboxylate 3651,1-dimethylethyl 2-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- Cyl}phenyl)carbonyl]amino}methyl)pyrrolidine-1-carboxylate 3663-amino-N-methyl-6-(3-{[(pyrrolidin-3- Bylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3673-amino-N-methyl-6-(3-{[(pyrrolidin-2- Bylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3683-amino-6-(2-fluoro-5-{[(phenylmethyl)amino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 3693-amino-6-{3-[(1,3-benzodioxol-5-ylacetyl)amino]phenyl}-N- Bmethylpyrazine-2-carboxamide 3703-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 3713-amino-6-{3-[({[3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-B N-methylpyrazine-2-carboxamide 3723-amino-N-methyl-6-{3-[(phenylmethyl)amino]phenyl}pyrazine-2- Bcarboxamide 373 3-amino-N-methyl-6-(3-{[({2-[(2-morpholin-4- Bylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide374 3-amino-N-methyl-6-{3-[({[4-(1- Bmethylethyl)phenyl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide375 3-amino-6-[3-({[(4-butylphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3763-amino-N-methyl-6-{3-[({[4-(1,2,3-thiadiazol-4- Ayl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3773-amino-N-methyl-6-{3-[({[4-(2- Athienyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3783-amino-6-{3-[({[4-(1,1- Bdimethylethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 379 3-amino-N-methyl-6-{3-[({[4-(1H-pyrazol-1- Byl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3803-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6- Bylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3813-amino-6-[3-({[(2-amino-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B methylpyrazine-2-carboxamide 3823-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]methyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 3833-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]methyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 3843-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]methyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 3853-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-2- Byl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3863-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6- Bylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3873-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N- Amethylpyrazine-2-carboxamide 3883-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 3893-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 390 3-amino-N-methyl-6-[3-({[(2-pyridin-4-B ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3913-amino-N-methyl-6-[3-({[(2-pyridin-3- Bylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3923-amino-N-methyl-6-{3-[({[4- B(methylsulfonyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 3933-amino-6-(3-{[(2,2-diphenylethyl)amino]methyl}phenyl)-N-methylpyrazine-B 2-carboxamide 3943-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-3- Byl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 3953-amino-N-methyl-6-{3-[({[3- B(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 3963-amino-6-[3-({[(4-aminophenyl)methyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 397 3-amino-N-methyl-6-{3-[({[4- B(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 3983-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)methyl]phenyl}-N-B methylpyrazine-2-carboxamide 3993-amino-6-[3-({[(2-fluorophenyl)methyl]amino}methyl)phenyl]-N- Amethylpyrazine-2-carboxamide 4003-amino-6-[5-({[(2,6-difluorophenyl)methyl]amino}carbonyl)pyridin-3-yl]-N-B methylpyrazine-2-carboxamide 4013-amino-6-(5-{[(biphenyl-2-ylmethyl)amino]carbonyl}pyridin-3-yl)-N- Bmethylpyrazine-2-carboxamide 4023-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 4033-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6- Bylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4043-amino-N-methyl-6-[3-({[(2-piperidin-1- Bylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4053-amino-6-{3-[({[4-fluoro-2- B(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 4063-amino-N-methyl-6-{3-[({[6-(trifluoromethyl)pyridin-3- Byl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 4073-amino-6-[3-(1H-benzimidazol-2-yl)phenyl]-N-methylpyrazine-2- Bcarboxamide 4083-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 4093-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N- Amethylpyrazine-2-carboxamide 4103-amino-N-methyl-6-{3-[(2-phenylethyl)amino]phenyl}pyrazine-2- Bcarboxamide 411 3-amino-6-(5-{[(2,3-dihydro-1,4-benzodioxin-6- Bylmethyl)amino]carbonyl}pyridin-3-yl)-N-methylpyrazine-2-carboxamide 4123-amino-N-methyl-6-[3-({[2- B(phenylamino)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 4133-amino-6-[3-({[(4-ethylphenyl)methyl]amino}carbonyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 414 3-amino-N-methyl-6-[3-({[(4-pyridin-3-B ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 4153-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)methyl]phenyl}-N- Amethylpyrazine-2-carboxamide 4163-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylmethyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 4173-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 4183-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- Amethylpyrazine-2-carboxamide 419 3-amino-N-methyl-6-[3-({[(3,4,5- Atrifluorophenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4203-amino-N-methyl-6-[3-({[(1R)-1- Bphenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4213-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4223-amino-N-methyl-6-{3-[({[4-(2- Athienyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 4233-amino-N-methyl-6-{3-[({[3-(1,2,3-thiadiazol-4- Byl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 4243-amino-N-methyl-6-[3-({[(4- Bpropylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 4253-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-B methylpyrazine-2-carboxamide 426 3-amino-N-methyl-6-{3-[({[3- B(trifluoromethyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide 427 3-amino-N-methyl-6-[3-({[(1S)-1- Bphenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4283-amino-6-[3-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 429 methyl(2S)-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- Cyl}phenyl)methyl]amino}(phenyl)ethanoate 4303-amino-6-(3-{[2-(2,5-difluorophenyl)hydrazino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 4313-amino-N-methyl-6-(3-{[2-(2,3,5,6-tetrafluoro-4- Bmethylphenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide 4323-amino-6-(3-{[2-(2-fluorophenyl)hydrazino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 4333-amino-6-(3-{[2-(2,4-difluorophenyl)hydrazino]carbonyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 434 3-amino-N-methyl-6-(3-{[2-(2,3,5,6- Btetrafluorophenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide 4353-amino-N-methyl-6-[3-({[(5-methylpyrazin-2- Byl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4363-amino-N-methyl-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1- Aylamino]methyl}phenyl)pyrazine-2-carboxamide 4373-amino-N-methyl-6-[3-({[(3S)-1-(phenylmethyl)pyrrolidin-3- Byl]amino}methyl)phenyl]pyrazine-2-carboxamide 4383-amino-N-methyl-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3- Byl]amino}methyl)phenyl]pyrazine-2-carboxamide 4393-amino-6-(3-{[ethyl(phenylmethyl)amino]methyl}phenyl)-N- Bmethylpyrazine-2-carboxamide 440 3-amino-N-methyl-6-[3-({[(1S,2S)-2- Bphenylcyclopropyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4413-Amino-6-(3-benzylcarbamoyl-phenyl)-pyrazine-2-carboxylic acid Bmethylamide 4423-amino-N-methyl-6-[3-(4-phenyl-1H-imidazol-2-yl)phenyl]pyrazine-2- Bcarboxamide 443 3-amino-N-methyl-6-[3-({[(4- Bpropylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide 4443-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 4453-amino-N-methyl-6-(3-{[(2R)-1,2,3,4-tetrahydronaphthalen-2- Aylamino]methyl}phenyl)pyrazine-2-carboxamide 4463-amino-N-methyl-6-(3-{[(1-methyl-1- Bphenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 4473-amino-6-{3-[(9H-fluoren-9-ylamino)methyl]phenyl}-N-methylpyrazine-2- Ccarboxamide 4483-amino-N-methyl-6-{3-[(naphthalen-1-ylamino)methyl]phenyl}pyrazine-2- Bcarboxamide 4493-amino-6-[3-({[(3-fluorobiphenyl-4-yl)methyl]amino}methyl)phenyl]-N- Bmethylpyrazine-2-carboxamide 4503-amino-6-{3-[({[2-fluoro-4-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}-A N-methylpyrazine-2-carboxamide 4513-amino-6-[3-({[(2-fluoro-4-furan-2-ylphenyl)methyl]amino}methyl)phenyl]-A N-methylpyrazine-2-carboxamide 4523-amino-N-methyl-6-{3-[(naphthalen-2-ylamino)methyl]phenyl}pyrazine-2- Bcarboxamide 4533-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4543-amino-N-methyl-6-(3-{[(2S)-1,2,3,4-tetrahydronaphthalen-2- Aylamino]methyl}phenyl)pyrazine-2-carboxamide 455 methyl3-amino-6-(3-{[(4,7-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)pyrazine-2-carboxylate 4563-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-B N-methylpyrazine-2-carboxamide 4573-amino-6-{3-[({[2-fluoro-5-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}-B N-methylpyrazine-2-carboxamide 4583-amino-6-[3-({[(4-ethenyl-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-B methylpyrazine-2-carboxamide 4593-amino-6-(3-{[(4,7-difluoro-3-methyl-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4603-amino-N-methyl-6-[3-({[(1S,2R)-2-(methyloxy)-2,3-dihydro-1H-inden-1- Byl]amino}methyl)phenyl]pyrazine-2-carboxamide 4613-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyrazine-2-carboxamide 4623-amino-6-[3-({[(2S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2- Ayl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4633-amino-6-[3-({[(2R)-6-bromo-1,2,3,4-tetrahydronaphthalen-2- Byl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4643-amino-6-(3-{[(5-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyrazine-2-carboxamide 4653-amino-6-[3-({[(2S)-5-bromo-2,3-dihydro-1H-inden-2- Ayl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4663-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-A N-methylpyrazine-2-carboxamide 4673-amino-6-(3-{[(4-fluoro-1-hydroxy-2,3-dihydro-1H-inden-2- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4683-amino-N-methyl-6-[3-({[(1R,2S)-2-(methyloxy)-2,3-dihydro-1H-inden-1- Byl]amino}methyl)phenyl]pyrazine-2-carboxamide 4693-amino-6-(3-{[(4,7-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4703-amino-6-(3-{[(6-bromo-4-fluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4713-amino-N-methyl-6-(3-{[(3-oxo-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)pyrazine-2-carboxamide 4723-amino-6-(3-{[(5-furan-2-yl-2,3-dihydro-1H-inden-1- Ayl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4733-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyrazine-2-carboxamide 4743-amino-6-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4753-amino-6-(3-{[(6-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-A N-methylpyrazine-2-carboxamide 4763-amino-6-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4773-amino-6-(3-{[(5-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-A N-methylpyrazine-2-carboxamide 4783-amino-N-methyl-6-[3-({[5-(2-thienyl)-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]pyrazine-2-carboxamide 4793-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4803-amino-6-(3-{[(5-furan-3-yl-2,3-dihydro-1H-inden-1- Ayl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4813-amino-N-methyl-6-[3-({[5-(3-thienyl)-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]pyrazine-2-carboxamide 4823-amino-6-[3-({[(1S)-4-fluoro-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4833-amino-6-[3-({[(1S)-5,7-difluoro-2,3-dihydro-1H-inden-1- Byl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 4843-amino-6-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4853-amino-6-(3-{[(6-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyrazine-2-carboxamide 4863-amino-6-(3-{[(4,6-dichloro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 4873-amino-6-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-A N-methylpyrazine-2-carboxamide 4883-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- Bethylpyrazine-2-carboxamide 4893-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide 4903-amino-N-methyl-6-[3-({[(1S)-5-(2-thienyl)-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]pyrazine-2-carboxamide 4913-amino-N-methyl-6-(3-{[(5-phenyl-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)pyrazine-2-carboxamide 4923-amino-6-(3-{[(4-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-A N-methylpyrazine-2-carboxamide 4933-amino-N-methyl-6-(3-{[(4-phenyl-2,3-dihydro-1H-inden-1- Ayl)amino]methyl}phenyl)pyrazine-2-carboxamide 4943-amino-N-methyl-6-[3-({[4-(2-thienyl)-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]pyrazine-2-carboxamide 4953-amino-N-methyl-6-[3-({[6-(2-thienyl)-2,3-dihydro-1H-inden-1- Byl]amino}methyl)phenyl]pyrazine-2-carboxamide 4963-amino-N-methyl-6-[3-({[5-(4-methyl-2-thienyl)-2,3-dihydro-1H-inden-1-A yl]amino}methyl)phenyl]pyrazine-2-carboxamide 4973-amino-N-methyl-6-[3-({[(2R)-6-phenyl-1,2,3,4-tetrahydronaphthalen-2- Byl]amino}methyl)phenyl]pyrazine-2-carboxamide 4983-amino-N-methyl-6-naphthalen-2-ylpyrazine-2-carboxamide B 4993-amino-N-methyl-6-{3-[({(1S,2S)-2- B[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide 5003-amino-6-{3-[(cyclopentylamino)methyl]phenyl}-N-methylpyrazine-2- Bcarboxamide 5013-amino-6-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyrazine-2-carboxamide 5023-amino-6-(3-{[(7-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyrazine-2-carboxamide 5033-amino-N-methyl-6-quinolin-3-ylpyrazine-2-carboxamide C 5043-amino-6-[3-(1H-imidazol-1-ylmethyl)phenyl]-N-methylpyrazine-2- Bcarboxamide 5053-amino-N-methyl-6-{3-[({5-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-B inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide 5063-amino-N-methyl-6-{3-[({(1R,2R)-2- B[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide 5073-amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)methyl]phenyl}-N- Bmethylpyrazine-2-carboxamide 5083-amino-6-{3-[({5-[(cyanomethyl)oxy]-2,3-dihydro-1H-inden-1- Byl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 5092-amino-5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- Bmethylpyridine-3-carboxamide 5103-amino-N-methyl-6-[3-({[5-(4-methylphenyl)-2,3-dihydro-1H-inden-1- Byl]amino}methyl)phenyl]pyrazine-2-carboxamide 5113-amino-6-[3-({[2-(dimethylamino)-1-phenylethyl]amino}methyl)phenyl]-N-B methylpyrazine-2-carboxamide 5123-amino-N-methyl-6-[3-({[5-(1H-1,2,4-triazol-1-yl)-2,3-dihydro-1H-inden-1-B yl]amino}methyl)phenyl]pyrazine-2-carboxamide 5133-amino-6-(3-{[(5-hydroxy-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 5143-amino-N-methyl-6-{3-[({4-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-B inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide 5153-amino-6-(3-{[(4-hydroxy-2,3-dihydro-1H-inden-1- Ayl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 5163-amino-N-methyl-6-{1-[(phenylmethyl)amino]isoquinolin-7-yl}pyrazine-2-C carboxamide 517 3-amino-N-methyl-6-(3-{[(2-morpholin-4-yl-1- Cphenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 5183-amino-N-methyl-6-(3-{[(1-phenyl-2-pyrrolidin-1- Bylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 5192-amino-5-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyridine-3-carboxamide 5202-amino-5-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5212-amino-5-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1- Cyl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5222-amino-5-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-B N-methylpyridine-3-carboxamide 5232-amino-5-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5242-amino-5-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1- Byl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide 5253-amino-6-{1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]isoquinolin-7-yl}-N- Bmethylpyrazine-2-carboxamide 5263-amino-6-{3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,3-dihydro-1H-inden-A 5-yl}-N-methylpyrazine-2-carboxamide 5273-amino-6-[3-({[6-(3-hydroxypropyl)-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 5285-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(1,3-oxazol-C 5-yl)pyrazin-2-amine 529 3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Bylamino]methyl}phenyl)pyrazine-2-carbohydrazide 5303-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Bylamino]methyl}phenyl)pyrazine-2-carboxamide 5311-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Bylamino]methyl}phenyl)pyrazin-2-yl]ethanone 5323-amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)methyl]phenyl}-N- D(naphthalen-2-ylmethyl)pyrazine-2-carboxamide 5333-amino-N-cyclohexyl-6-{3-[(2,3-dihydro-1H-inden-1- Cylamino)methyl]phenyl}pyrazine-2-carboxamide 5343-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- C(pyridin-4-ylmethyl)pyrazine-2-carboxamide 535{3-[5-amino-6-(4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol C 5365-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4H-1,2,4- Btriazol-3-yl)pyrazin-2-amine 5373-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- C(2,2,2-trifluoroethyl)pyrazine-2-carboxamide 5383-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(5-C hydroxypentyl)pyrazine-2-carboxamide 5393-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(4-B hydroxybutyl)pyrazine-2-carboxamide 5403-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-B pyrrolidin-1-ylethyl)pyrazine-2-carboxamide 5413-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-C piperidin-1-ylethyl)pyrazine-2-carboxamide 5423-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-C morpholin-4-ylethyl)pyrazine-2-carboxamide 5433-amino-N-(cyclopropylmethyl)-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Bylamino}methyl}phenyl)pyrazine-2-carboxamide 5443-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- C(phenylmethyl)pyrazine-2-carboxamide 5453-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-C phenylethyl)pyrazine-2-carboxamide 546[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Bylamino]methyl}phenyl)pyrazin-2-yl](phenyl)methanone 5473-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-B hydroxyethyl)pyrazine-2-carboxamide 5483-amino-N-cyclopropyl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Bylamino]methyl}phenyl)pyrazine-2-carboxamide 5495-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(pyrrolidin-1-C ylcarbonyl)pyrazin-2-amine 550{3-[5-amino-6-(5-methyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanolC 551{3-[5-amino-6-(5-phenyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanolB 552 (3-{5-amino-6-[5-(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2- Cyl}phenyl)methanol 5533-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N′- Bmethylpyrazine-2-carbohydrazide 5543-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N,N- Bdimethylpyrazine-2-carboxamide 5555-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5- B(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine 5563-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-B (dimethylamino)ethyl]pyrazine-2-carboxamide 5575-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-phenyl- A1H-1,2,4-triazol-5-yl)pyrazin-2-amine 5583-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-A (1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide 5593-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-A (methylamino)ethyl]pyrazine-2-carboxamide 5603-{5-amino-6-[(3-fluorophenyl)carbonyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 5613-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-B hydroxypropyl)pyrazine-2-carboxamide 562 1,1-dimethylethyl4-({[3-amino-6-(3- D {[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate 563 1,1-dimethylethyl4-[({[3-amino-6-(3- D {[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]piperidine-1-carboxylate 5643-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-piperidin-4- Bylpyrazine-2-carboxamide 5653-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-(piperidin-4- Bylmethyl)pyrazine-2-carboxamide 5663-[5-amino-6-(morpholin-4-ylcarbonyl)pyrazin-2-yl]-N- C(phenylmethyl)benzamide 567 1,1-dimethylethyl 3-({[3-amino-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 5683-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-pyrrolidin-3- Bylpyrazine-2-carboxamide 569(3-{5-amino-6-[5-(1,1-dimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2- Cyl}phenyl)methanol 570{3-[5-amino-6-(5-furan-2-yl-4H-1,2,4-triazol-3-yl)pyrazin-2- Byl]phenyl}methanol 571[3-(5-amino-6-{5-[3-(methyloxy)phenyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-D yl)phenyl]methanol 5722-({3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2-yl}carbonyl)-N- Bphenylhydrazinecarboxamide 5733-{5-amino-6-[(4-methylpiperazin-1-yl)carbonyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 5743-(5-amino-6-{[4-(4-fluorophenyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-D (phenylmethyl)benzamide 5753-(5-amino-6-{[4-(phenylmethyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-D (phenylmethyl)benzamide 576 methylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Cyl]carbonyl}glycinate 577N-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}glycine 5783-{5-amino-6-[(3,5-difluorophenyl)carbonyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 5793-[5-amino-6-(biphenyl-4-ylcarbonyl)pyrazin-2-yl]-N- D(phenylmethyl)benzamide 580{3-[5-amino-6-(3-pyridin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Byl]phenyl}methanol 581(3-{5-amino-6-[3-(4-chlorophenyl)-1H-1,2,4-triazol-5-yl]pyrazin-2- Dyl}phenyl)methanol 5825-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1,1- Bdimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine 583(3-{5-amino-6-[3-(2-thienyl)-1H-1,2,4-triazol-5-yl]pyrazin-2- Byl}phenyl)methanol 5845-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[3- B(methyloxy)phenyl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 5853-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-C (dimethylamino)propyl]pyrazine-2-carboxamide 5863-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-B (1H-imidazol-1-yl)propyl]pyrazine-2-carboxamide 5873-{5-amino-6-[(4-chloro-3-fluorophenyl)carbonyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 5883-(5-amino-6-{[2,4-bis(methyloxy)phenyl]carbonyl}pyrazin-2-yl)-N- D(phenylmethyl)benzamide 5893-(5-amino-6-{[4-(dimethylamino)phenyl]carbonyl}pyrazin-2-yl)-N- D(phenylmethyl)benzamide 590 methyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}-L-prolinate 591 methyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}piperidine-3-carboxylate 592 1,1-dimethylethyl4-{[3-amino-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperazine-1-carboxylate 593 3-[5-amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-yl]-N- D(phenylmethyl)benzamide 594N-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Cyl]carbonyl}glutamic acid 5955-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{5- C[(methyloxy)methyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-amine 5965-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-3-A yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 5973-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-A (methylamino)propyl]pyrazine-2-carboxamide 5983-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-C pyrrolidin-1-ylpropyl)pyrazine-2-carboxamide 5993-(5-amino-6-{(1E)-N-[4-(methyloxy)phenyl]ethanehydrazonoyl}pyrazin-2- Cyl)-N-(phenylmethyl)benzamide 6003-(5-amino-6-{(1E)-N-[4-(1-methylethyl)phenyl]ethanehydrazonoyl}pyrazin-C 2-yl)-N-(phenylmethyl)benzamide 6013-{5-amino-6-[(1E)-N-1,3-benzothiazol-2-ylethanehydrazonoyl]pyrazin-2- Dyl}-N-(phenylmethyl)benzamide 6023-{5-amino-6-[(1E)-N-(4-methylphenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-D (phenylmethyl)benzamide 6033-{5-amino-6-[(1E)-N-(4-chlorophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-D (phenylmethyl)benzamide 6043-{5-amino-6-[(1E)-N-methyl-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N- C(phenylmethyl)benzamide 6053-{5-amino-6-[(1E)-N-(2-hydroxyethyl)ethanehydrazonoyl]pyrazin-2-yl}-N-B (phenylmethyl)benzamide 606{3-[5-amino-6-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Ayl]phenyl}methanol 607{3-[5-amino-6-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Cyl]phenyl}methanol 6083-[5-amino-6-(2-aminopyrimidin-4-yl)pyrazin-2-yl]-N- C(phenylmethyl)benzamide 6093-{5-amino-6-[2-(dimethylamino)pyrimidin-4-yl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 610 ethylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}-L-tyrosinate 611N-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}-D-tyrosine 612 1,1-dimethylethyl [3-({[3-amino-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)propyl]carbamate 613 3-amino-N-(3-aminopropyl)-6-(3- B{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6141-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}piperidine-3-carboxylic 615 1,1-dimethylethyl[2-({[3-amino-6-(3- D {[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)ethyl]carbamate 616 3-amino-N-(2-aminoethyl)-6-(3- B{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6171,1-dimethylethyl (1-{[3-amino-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidin-4-yl)carbamate 6183-{5-amino-6-[(4-aminopiperidin-1-yl)carbonyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6193-{5-amino-6-[imino(2-phenylhydrazino)methyl]pyrazin-2-yl}-N- C(phenylmethyl)benzamide 6203-{5-amino-6-[imino(morpholin-4-ylamino)methyl]pyrazin-2-yl}-N- C(phenylmethyl)benzamide 6213-(5-amino-6-{imino[(4-methylpiperazin-1-yl)amino]methyl}pyrazin-2-yl)-N-D (phenylmethyl)benzamide 6223-{5-amino-6-[imino(piperidin-1-ylamino)methyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6233-{5-amino-6-[(azepan-1-ylamino)(imino)methyl]pyrazin-2-yl}-N- C(phenylmethyl)benzamide 6243-{5-amino-6-[imino({(2R)-2-[(methyloxy)methyl]pyrrolidin-1- Dyl}amino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide 625{3-[5-amino-6-(3-piperidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Byl]phenyl}methanol 6263-{5-amino-6-[(1E)-N-morpholin-4-ylethanimidoyl]pyrazin-2-yl}-N- C(phenylmethyl)benzamide 6274-((2E)-2-{1-[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-C 2-yl]ethylidene}hydrazino)benzoic acid 628 ethyl((2E)-2-{1-[3-amino-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]ethylidene}hydrazino)acetate 6293-{5-amino-6-[(1E)-N,N-dimethylethanehydrazonoyl]pyrazin-2-yl}-N- B(phenylmethyl)benzamide 630 3-(5-amino-6-{(1E)-N-[4- D(methylsulfonyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6313-{5-amino-6-[(1E)-N-(4-cyanophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6323-{5-amino-6-[(1E)-N-pyridin-2-ylethanehydrazonoyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6333-(5-amino-6-{(1E)-N-[amino(imino)methyl]ethanehydrazonoyl}pyrazin-2- Cyl)-N-(phenylmethyl)benzamide 634 3-[5-amino-6-((1E)-N-{4- D[(trifluoromethyl)oxy]phenyl}ethanehydrazonoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6353-(5-Amino-6-{1-[(4-nitro-phenyl)-hydrazono]-ethyl}-pyrazin-2-yl)-N-benzyl-D benzamide 636 3-(5-amino-6-{(1E)-N-[4-(trifluoromethyl)pyrimidin-2- Cyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6373-{5-amino-6-[(1E)-N-1H-1,2,3-benzotriazol-1-ylethanimidoyl]pyrazin-2-yl}-D N-(phenylmethyl)benzamide 6383-{5-amino-6-[(1E)-N-methylethanehydrazonoyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6395-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-piperidin-B 4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 6403-(5-amino-6-{(1E)-N-[4- D(trifluoromethyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 6413-{5-amino-6-[(1E)-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N- C(phenylmethyl)benzamide 6423-{5-amino-6-[(1E)-N-(4-methylpiperazin-1-yl)ethanimidoyl]pyrazin-2-yl}-N-B (phenylmethyl)benzamide 643{3-[5-amino-6-(3-pyrrolidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Byl]phenyl}methanol 6443-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- A[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 6453-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- B[(3R)-pyrrolidin-3-yl]pyrazine-2-carboxamide 6463-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- C[(3S)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamide 647N-[3-(acetylamino)propyl]-3-amino-6-(3- C{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6483-amino-N-{3-[(furan-2-ylcarbonyl)amino]propyl}-6-(3- C{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6493-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- D[(3S)-1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamide 6503-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-4- Cylcarbonyl)amino]propyl}pyrazine-2-carboxamide 651N-[3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}amino)propyl]quinoxaline-2-carboxamide 6523-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[3-({[6- D(trifluoromethyl)pyridin-3-yl]carbonyl}amino)propyl]pyrazine-2-carboxamide6533-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(quinolin-8- Dylsulfonyl)amino]propyl}pyrazine-2-carboxamide 6543-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-2- Cylsulfonyl)amino]propyl}pyrazine-2-carboxamide 6553-amino-N-[3-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)propyl]-C 6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6563-[5-amino-6-(2-methylpyrimidin-4-yl)pyrazin-2-yl]-N- C(phenylmethyl)benzamide 6573-{5-amino-6-[2-(methylamino)pyrimidin-4-yl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6583-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-4- Cylcarbonyl)amino]ethyl}pyrazine-2-carboxamide 6593-amino-N-{2-[(furan-2-ylcarbonyl)amino]ethyl}-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 660N,N′-cyclohexane-1,2-diylbis[3-amino-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide] 661N-[2-(acetylamino)ethyl]-3-amino-6-(3- C{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6623-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(quinolin-8- Dylsulfonyl)amino]ethyl}pyrazine-2-carboxamide 663N-[2-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}amino)ethyl]quinoxaline-2-carboxamide 6643-amino-N-(2-{[(2-chloropyridin-3-yl)carbonyl]amino}ethyl)-6-(3- C{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6653-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-2- Dylsulfonyl)amino]ethyl}pyrazine-2-carboxamide 6663-amino-N-[2-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)ethyl]-6-C (3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6673-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2- Bcarboxamide 668 3-[5-amino-6-(imino{2-[4-(trifluoromethyl)pyrimidin-2- Cyl]hydrazino}methyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6693-{5-amino-6-[[2-(1,3-benzothiazol-2-yl)hydrazino](imino)methyl]pyrazin-2-D yl}-N-(phenylmethyl)benzamide 6703-[5-amino-6-(1,5-diphenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N- D(phenylmethyl)benzamide 6713-[5-amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N- C(phenylmethyl)benzamide 6723-[5-amino-6-(1-methyl-5-phenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N- D(phenylmethyl)benzamide 6733-[5-amino-6-((1E)-N-{(2R)-2-[(methyloxy)methyl]pyrrolidin-1- Byl}ethanimidoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide 6743-{5-amino-6-[(1E)-N-azepan-1-ylethanimidoyl]pyrazin-2-yl}-N- B(phenylmethyl)benzamide 6753-(5-amino-6-{(E)-[(phenylmethyl)hydrazono]methyl}pyrazin-2-yl)-N- D(phenylmethyl)benzamide 6763-[5-amino-6-((E)-{[amino(imino)methyl]hydrazono}methyl)pyrazin-2-yl]-N-D (phenylmethyl)benzamide 6773-(5-amino-6-{(E)-[(2-hydroxyethyl)hydrazono]methyl}pyrazin-2-yl)-N- C(phenylmethyl)benzamide 6783-{5-amino-6-[(E)-(pyridin-2-ylhydrazono)methyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6793-(5-amino-6-{(E)-[(4-cyanophenyl)hydrazono]methyl}pyrazin-2-yl)-N- D(phenylmethyl)benzamide 6803-(5-amino-6-{(E)-[(4-methylphenyl)hydrazono]methyl}pyrazin-2-yl)-N- D(phenylmethyl)benzamide 6813-{5-amino-6-[(E)-(hydroxyimino)methyl]pyrazin-2-yl}-N- C(phenylmethyl)benzamide 682{3-[5-amino-6-(3-pyridin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Cyl]phenyl}methanol 6835-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-piperidin-A 3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 6843-amino-N-[3-({[4-(dimethylamino)phenyl]carbonyl}amino)propyl]-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6853-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N- A[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 686 1,1-dimethylethyl4-[(3S)-3-({[3-amino-6-(3- C{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]piperidine-1-carboxylate 6873-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-piperidin-C 4-ylpyrrolidin-3-yl]pyrazine-2-carboxamide 688 1,1-dimethylethyl(2R)-2-{[(3S)-3-({[3-amino-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]methyl}pyrrolidine-1-carboxylate 6893-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{(3S)-1-[(2R)- Cpyrrolidin-2-ylmethyl]pyrrolidin-3-yl}pyrazine-2-carboxamide 6903-amino-N-((3S)-1-{[4-(dimethylamino)phenyl]methyl}pyrrolidin-3-yl)-6-(3-C {[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6913-amino-N-{2-[({[4-(dimethylamino)phenyl]amino}carbonyl)amino]ethyl}-6-D (3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6923-amino-N-[2-({[4-(dimethylamino)phenyl]carbonyl}amino)ethyl]-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 6933-{5-amino-6-[imino(2-pyridin-2-ylhydrazino)methyl]pyrazin-2-yl}-N- D(phenylmethyl)benzamide 6943-[5-amino-6-(morpholin-4-ylmethyl)pyrazin-2-yl]-N- D(phenylmethyl)benzamide 695 ethyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]methyl}piperidine-4-carboxylate 6963-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-(pyridin-2-B ylmethyl)pyrrolidin-3-yl]pyrazine-2-carboxamide 697 methylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2- Dyl]carbonyl}threoninate 698{3-[5-amino-6-(3-piperidin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Dyl]phenyl}methanol 6993-(ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3- D{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 7003-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3- B{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 7013-[5-amino-6-(1-methyl-5-piperidin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-D N-(phenylmethyl)benzamide 7023-[5-amino-6-(5-methyl-1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-C (phenylmethyl)benzamide 703{3-[5-amino-6-(3-morpholin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2- Byl]phenyl}methanol 7045-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3S)- Apiperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 7055-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3R)- Apiperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 7063-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- B[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide 7076-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-3- D(ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide 7083-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1- Byl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide709 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 710 1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-({[(1R)-1- Dphenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 711 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(3,4-dihydroisoquinolin-2(1H)- Dylcarbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate712 1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(2- Dphenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 713 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(1S)-1- Cphenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 7143-amino-6-[3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)phenyl]-N-[(3S)- Bpyrrolidin-3-yl]pyrazine-2-carboxamide 7153-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-B yl]pyrazine-2-carboxamide 7163-amino-6-[(3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)- Cpyrrolidin-3-yl]pyrazine-2-carboxamide 7173-amino-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)- Bpyrrolidin-3-yl]pyrazine-2-carboxamide 7183-{5-amino-6-[(2-ethylhydrazino)(imino)methyl]pyrazin-2-yl}-N-(2,3- Cdihydro-1H-inden-1-yl)benzamide 7193-{5-amino-6-[imino(2-methylhydrazino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-C dihydro-1H-inden-1-yl)benzamide 7203-{5-amino-6-[imino(2-phenylhydrazino)methyl)]pyrazin-2-yl}-N-[(1S)-2,3-D dihydro-1H-inden-1-yl]benzamide 721 phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 722 phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 7235-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-4-A yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 724[3-(5-amino-6{3-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2- Byl)phenyl]methanol 725[3-(5-amino-6-{3[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2- Byl)phenyl]methanol 7263-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide7273-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1S,2R)-2-hydroxy-2,3- Cdihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 7281,1-dimethylethyl 3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate 7293-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- Apiperidin-3-ylpyrazine-2-carboxamide 7303-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- B(1-ethylpiperidin-3-yl)pyrazine-2-carboxamide 7313-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1R,2S)-2-hydroxy-2,3- Bdihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 732(3-{5-amino-6-[5-(1-ethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-C yl}phenyl)methanol 7335-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1- Bethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine 7343-[5-amino-6-(1-ethyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-B [(1R)-2,3-dihydro-1H-inden-1-yl]benzamide 7353-(5-amino-6-(1-methyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-B N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 736(3-{5-amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-C yl}phenyl)methanol 7375-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[3-(1- Bmethylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-amine 7381,1-dimethylethyl (3S)-3-{[(3-amino-6-{3-[({[4- B(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 739 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[({4- B[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 740 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2-chloro-6- Cfluorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 741 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[4- C(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 742 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[(2,3-dihydro-1H-inden-2- Bylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 7433-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N- B[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7443-amino-N-[(3S)-pyrrolidin-3-yl]-6-(3-{[({4- A[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 7453-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N-[(3S)-B pyrrolidin-3-yl]pyrazine-2-carboxamide 7463-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-B [(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7473-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}-N- A[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7483-{5-amino-6-[imino(2-pyridin-4-ylhydrazino)methyl]pyrazin-2-yl}-N-[(1R)-C 2,3-dihydro-1H-inden-1-yl]benzamide 749 phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 7503-amino-6-(3-{(1S)-1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]ethyl}phenyl)-B N-methylpyrazine-2-carboxamide 7513-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Byl]amino}carbonyl)phenyl]-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide 752 1,1-dimethylethyl(3S)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrrolidine-1-carboxylate 7533-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- A[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide 754 phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Cylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate 7553-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-A [(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 756 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(4- Bchlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 757 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(pyridin-2- Cylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 758 1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(pyridin-3- Cylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 759 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[(3,4-dihydro-2H-chromen-4- Cylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 7603-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apyrrolidin-3-yl]pyrazine-2-carboxamide 7613-amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)- Bpyrrolidin-3-yl]pyrazine-2-carboxamide 7623-amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)- Bpyrrolidin-3-yl]pyrazine-2-carboxamide 763 dimethyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzene-1,3- Cdicarboxylate 7643-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 7653-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- A[(3R)-piperidin-3-yl]pyrazine-2-carboxamide 7663-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}carbonyl)phenyl]-N-piperidin-3-ylpyrazine-2-carboxamide 7673-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- B[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide 7683-amino-N-azepan-4-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Bylamino]carbonyl}phenyl)pyrazine-2-carboxamide 769 1,1-dimethylethyl(3S)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro- D1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate 770 1,1-dimethylethyl4-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)azepane-1-carboxylate 7713-[5-amino-6-(5-{2-[(phenylmethyl)oxy]ethyl}-1H-1,2,4-triazol-3-yl)pyrazin-C 2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 7723-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-4- Bfluorophenyl)-N-methylpyrazine-2-carboxamide 7733-[5-amino-6-(1-phenyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-B N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 7743-{5-amino-6-[amino(imino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H- Cinden-1-yl]benzamide 7753-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-A [(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]benzamide 7761,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-B ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate 777 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro- A1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate 7783-amino-6-{3-[(3,4-dihydro-2H-chromen-4-ylamino)carbonyl]phenyl}-N- B[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7793-amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)carbonyl]phenyl}-N- B[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 7803-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}carbonyl)phenyl]-N-[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide 781 1,1-dimethylethyl4-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H- Binden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]azepane-1-carboxylate 7823-amino-N-azepan-4-yl-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-A yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 7833-amino-N-azepan-4-yl-6-{3-[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2- Bd][1,3]oxazol-2-yl]phenyl}pyrazine-2-carboxamide 784 1,1-dimethylethyl(3R)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Dylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrolidine-1-carboxylate 7853-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- A[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide 786 1,1-dimethylethyl(3R)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro- D1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate 7873-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide 7883-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-5- Bfluorophenyl)-N-methylpyrazine-2-carboxamide 7893-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5- C[(methyloxy)carbonyl]benzoic acid 790 methyl3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-{[(1S)-2,3- Bdihydro-1H-inden-1-ylamino]carbonyl}benzoate 7915-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-B inden-1-yl]-N′-pyrrolidin-3-ylbenzene-1,3-dicarboxamide 7923-[5-amino-6-(5-phenyl-1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-C (phenylmethyl)benzamide 7933-[5-amino-6-(5-methyl-1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-C [(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 794 1,1-dimethylethyl(3R)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Cylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate 795 1,1-dimethylethyl(3R)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro- D1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate 7963-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 7975-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-[(1R)-2,3-dihydro-1H-B inden-1-yl]-N′-[(3R)-pyrrolidin-3-yl]benzene-1,3-dicarboxamide 798(3-{5-amino-6-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-B yl}phenyl)methanol 7993-[5-amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-D dihydro-1H-inden-1-yl]benzamide 800 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1-methyl-1- Dphenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 8013-amino-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)- Bpyrrolidin-3-yl]pyrazine-2-carboxamide 8023-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Cylamino]sulfonyl}phenyl)pyrazine-2-carboxamide 8033-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)-N- Bpiperidin-3-ylpyrazine-2-carboxamide 8043-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- B[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide 8053-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Byl]amino}carbonyl)phenyl]-N-[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide 8063-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide807 3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide8083-amino-N-[(3S)pyrrolidin-3-yl]-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-A ylamino]methyl}phenyl)pyrazine-2-carboxamide 809N-[3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-A yl)phenyl]-2-(2,4-dichlorophenyl)acetamide 810 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1- Dylamino]sulfonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 8113-amino-6-(3-hydroxyphenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2- Bcarboxamide 8123-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)-N- B[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8133-[5-amino-6-(1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-C dihydro-1H-inden-1-yl]benzamide 8143-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(3,4,5- Atrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8153-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,6- Btrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8163-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,5- Btrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8173-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8183-{5-amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}-C N-[(2-chloro-6-fluorophenyl)methyl]benzamide 8193-amino-N-1-azabicyclo[2.2.2]oct-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-B ylamino]methyl}phenyl)pyrazine-2-carboxamide 8203-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-A [(4-chloro-2-fluorophenyl)methyl]benzamide 8213-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-A [(2-chlorophenyl)methyl]benzamide 822 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2,4- Cdichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 823 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(3,4- Cdichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 8245-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4-piperidin-D 3-yl-1,3-thiazol-2-yl)pyrazin-2-amine 8253-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8263-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 8273-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-B [(2,6-difluorophenyl)methyl]benzamide 8283-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-B [(2-chloro-6-fluorophenyl)methyl]benzamide 8293-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-B [(2,5-dichlorophenyl)methyl]benzamide 8303-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-A [(3,4-dichlorophenyl)methyl]benzamide 8313-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8323-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 833 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[(1,1- Bdimethylethyl)oxy]carbonyl}amino)methyl]phenyl}pyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate 8343-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-A [(2-fluorophenyl)methyl]benzamide 8353-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-A [(3-fluorophenyl)methyl]benzamide 8363-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-A [(4-fluorophenyl)methyl]benzamide 8373-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-A [(3-chlorophenyl)methyl]benzamide 8383-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-A [(4-chlorophenyl)methyl]benzamide 8393-amino-6-[3-(aminomethyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2- Acarboxamide 8403-amino-6-(3-hydroxyphenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2- Acarboxamide 841 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2- Byl}carbonyl)amino]piperidine-1-carboxylate 8423-amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8433-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4- A[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 8443-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8453-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-5- Ayl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 8463-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2- A[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 8473-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8483-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 8493-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8503-amino-6-{3-[({[4-fluoro-3- A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8513-amino-6-(3-{[(naphthalen-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8523-amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8533-amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8543-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(2- Athienyl)phenyl]methyl}amino)carbonyl]phenyl}pyazine-2-carboxamide 8553-amino-6-{3-[({[2-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8563-amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8573-amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8583-amino-6-[3-({[(2,3-difluoro-4- Amethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8593-amino-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8603-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6- Aylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8613-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8623-amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8633-amino-N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6(3-{[(1S)-2,3-dihydro-1H-B inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide 8643-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8653-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-A [(2,4-difluorophenyl)methyl]benzamide 8663-amino-6-(3-{[(1,2-diphenylethyl)amino]carbonyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8673-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-A [(3,4-difluorophenyl)methyl]benzamide 8683-amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 869 methyl4-[({[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2- Ayl)phenyl]carbonyl}amino)methyl]benzoate 8703-amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8713-amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8723-amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 873 3-amino-6-{3-[({[4-fluoro-2- A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 874 3-amino-6-{3-[({[2-fluoro-3- A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8753-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3R)-pyrrolidin-3- Aylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 8763-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(3R)-pyrrolidin-3- Aylamino]carbonyl}phenyl)pyrazine-2-carboxamide 8773-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-piperidin-1- Aylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 8783-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-A yl]pyrazine-2-carboxamide 8793-amino-6-[3-({[2-(methyloxy)ethyl]amino}carbonyl)phenyl]-N-[(3S)- Bpiperidin-3-yl]pyrazine-2-carboxamide 8803-amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8813-amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8823-amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8833-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4- A[(trifluoromethyl)oxy]phenyl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 8843-amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8853-amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-A yl]pyrazine-2-carboxamide 8863-amino-6-(3-{[(2,6-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-A 3-yl]pyrazine-2-carboxamide 8873-amino-6-(3-{[(pentafluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-A 3-yl]pyrazine-2-carboxamide 8883-amino-6-(3-{[(2-chloro-4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8893-amino-6-[3-({[4-(methylthio)phenyl]acetyl}amino)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8903-amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-A 3-yl]pyrazine-2-carboxamide 8913-amino-6-[3-({[4-(4-chlorophenyl)-2-thienyl]carbonyl}amino)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 8923-amino-6-[3-({[(4-bromophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8933-amino-6-(3-{[(naphthalen-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 8943-amino-6-(3-{[2-(4-phenylpiperazin-1-yl)ethyl]oxy}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 895N-[(3-{5-amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-A (4-bromophenyl)urea 896N-[(3-{5-amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-A naphthalen-2-ylurea 8973-amino-6-(3-{[(2,4-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-A 3-yl]pyrazine-2-carboxamide 8983-amino-6-(3-{[(2-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-A yl]pyrazine-2-carboxamide 8993-amino-6-{3-[({5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2- Ayl}carbonyl)amino]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide9003-amino-6-[3-({[4-(dimethylamino)naphthalen-1-yl]carbonyl}amino)phenyl]-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9013-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4-(1,2,3-thiadiazol-5- Ayl)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 9023-amino-6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9033-amino-6-{3-[({[4-(dimethylamino)phenyl]carbonyl}amino)methyl]phenyl}-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9043-amino-6-{3-[(2-hydroxyethyl)oxy]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-A 2-carboxamide 905 3-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5- Aylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 906 3-amino-6-(3-{[(3,4-dihydro-2H-1,5-benzodioxepin-7- Aylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 907 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(quinolin-7- Bylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9083-amino-6-[3-({[(biphenyl-4-ylamino)carbonyl]amino}methyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9093-amino-6-(3-{[(4-bromo-2-fluorophenyl)carbonyl]amino}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 910N-[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2- Ayl)phenyl]quinoline-3-carboxamide 9113-amino-6-[3-({[6-(methyloxy)-1-benzofuran-3-yl]acetyl}amino)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9123-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4′-(trifluoromethyl)biphenyl-2-A yl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 9133-amino-6-[3-({[3,5-bis(trifluoromethyl)phenyl]acetyl}amino)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9143-amino-6-{3-[({[(2,4-difluorophenyl)amino]carbonyl}amino)methyl]phenyl}-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9153-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2- B(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide 916 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4- B[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 917 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2- B[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 918 3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4- B(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide 919 3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({2- B[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide 920 3-amino-6-(3-{[({[2- A(methylthio)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 921 3-amino-6-{3-[({[(3-bromo-5- Amethylphenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9223-amino-6-{3-[({[(2-bromophenyl)amino]carbonyl}amino)methyl]phenyl}-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9235-[3-(aminomethyl)phenyl]-3-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-A yl}pyrazin-2-amine 924 3-amino-6-{3-[({[4-(4-methylpiperazin-1- Ayl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9253-amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 9263-amino-6-(3-{[(2-morpholin-4-ylethyl)amino]carbonyl}phenyl)-N-[(3S)- Bpiperidin-3-yl]pyrazine-2-carboxamide 9273-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2R)-pyrrolidin-2- Aylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 9283-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2S)-pyrrolidin-2- Aylamino]carbonyl}phenyl)pyrazine-2-carboxamide 9293-amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-[(3S)-piperidin-3- Byl]pyrazine-2-carboxamide 9303-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4- A[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide 931 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({[4- A(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9323-amino-6-{3-[({[4-(methyloxy)phenyl]carbonyl}amino)methyl]phenyl}-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9333-amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 9343-amino-6-(3-{[(furan-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-A 3-yl]pyrazine-2-carboxamide 9353-amino-6-[3-({[(2,3-dihydro-1,4-benzodioxin-6- Aylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 936 3-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5- Aylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 937 3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6- Aylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 938 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2- Athienylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9393-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2- Aylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 940N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-A yl)phenyl]methyl}-2-chlorobenzamide 941N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-A yl)phenyl]methyl}-4-chlorobenzamide 942N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-A yl)phenyl]methyl}-4-iodobenzamide 943N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-A yl)phenyl]methyl}-3,5-difluorobenzamide 944N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-A yl)phenyl]methyl}-4-bromo-2-fluorobenzamide 945N-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-A yl)phenyl]methyl}-4-bromo-2-chlorobenzamide 9463-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]-5-(3-{[(1S)-2,3-dihydro-1H-A inden-1-ylamino]methyl}phenyl)pyrazin-2-amine 9473-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Aylamino]methyl}phenyl)pyrazine-2-carboxamide 9483-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2-(2-thienyl)-1,3-thiazol-4- Ayl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide 9493-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[5-(2-thienyl)pyridin-3- Ayl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide 9503-amino-6-{3-[({[4-(1,1- Adimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 951 3-amino-6-[3-({[(2,4-dichloro-6- Amethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9523-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9533-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2- Athienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9543-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(3- Athienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 9553-amino-6-[3-({[(4-chlorophenyl)sulfonyl]amino}methyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 9563-amino-6-[3-({[(1,3-benzodioxol-5- Aylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 957 3-amino-6-(3-{[({[4- A(methyloxy)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9583-amino-6-{3-[({[(4-fluorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9593-amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3- Ayl]pyrazine-2-carboxamide 9603-amino-6-{3-[(2-morpholin-4-ylethyl)oxy]phenyl}-N-[(3S)-piperidin-3- Byl]pyrazine-2-carboxamide 9613-amino-6-[3-(methyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2- Acarboxamide 9623-amino-6-[3-(ethyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2- Acarboxamide 9633-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-4- Ayl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 9643-amino-6-(3-{[2-(ethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3- Ayl]pyrazine-2-carboxamide 965 phenylmethyl4-(2-{[3-(5-amino-6-{[(3S)-piperidin-3- Aylamino]carbonyl}pyrazin-2-yl)phenyl]oxy}ethyl)piperazine-1-carboxylate966 3-amino-6-(3-{[({[4- A(dimethylamino)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9673-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1- Aylamino]carbonyl}phenyl)pyrazine-2-carboxamide 9683-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Ayl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazin-2-carboxamide 9693-amino-6-[3-({[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1- Cyl]amino}carbonyl)phenyl]-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide 9703-amino-N-[(3S)-azepan-3-yl]-6-[3({[(1S,2S)-2-hydroxy-2,3-dihydro-1H- Ainden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 9713-amino-6-{3-[({[(4-chlorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9723-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N- B[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide 9733-amino-N-[(3S)-azepan-3-yl]-6-(3{[(1S)-2,3-dihydro-1H-inden-1- Aylamino]carbonyl}phenyl)pyrazine-2-carboxamide 9743-amino-N-[(3S)-azepan-3-yl]-6-(3-methylphenyl)pyrazine-2-carboxamide A9753-amino-6-(3-{[(2-methylphenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-A yl]pyrazine-2-carboxamide 9763-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[3- A(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide 9773-amino-6-[3-({[4-(methyloxy)phenyl]acetyl}amino)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 9783-amino-6-(3-{[(6-(methylpyridin-3-yl)carbonyl]amino}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 9793-amino-6-(3-{[(3-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-A yl]pyrazine-2-carboxamide 9803-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3- Aylacetyl)amino]phenyl}pyrazine-2-carboxamide 9813-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3- Aylcarbonyl)amino]phenyl}pyrazine-2-carboxamide 9823-amino-6-(3-{[(2,5-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-A 3-yl]pyrazine-2-carboxamide 9833-amino-6-(3-{[(4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-A yl]pyrazine-2-carboxamide 984 3-amino-6-{3-[({[3-fluoro-5 A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9853-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9863-Amino-6-[3-({[5-(4-nitro-phenyl)-furan-2-carbonyl]-amino}-methyl)- Aphenyl]-pyrazine-2-carboxylic acid (3S)-piperidin-3-ylamide 9873-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9883-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4- A[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)phenyl]pyrazine-2-carboxamide 9893-amino-6-[3-({[(5-methylisoxazol-3-yl)carbonyl]amino}methyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9903-amino-6-(3-{[(isoxazol-5-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 9913-amino-6-[3-({[(4-methyl-1,2,3-thiadiazol-5- Ayl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9923-amino-6-[3-({[(2,5-dichloro-3-thienyl)carbonyl]amino}methyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9933-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9943-amino-6-{3-[({[(2-chloro-5 A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9953-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9963-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(4-chloro-2- Afluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 9973-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9983-amino-6-{3-[({[2-fluoro-5- A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 9993-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 10003-amino-6-[3-({[(3-chloro-2,6- Adifluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 1001 3-amino-6-{3-[({[(2-fluoro-4- A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10023-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10033-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10043-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,6- Atrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10053-amino-6-{3-[({[4-chloro-3- A(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10063-amino-6-[3-({[(3-chloro-4-fluorophenyl)methyl]amino}corbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10073-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,3- Adifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10083-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,4- Adifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10093-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,5- Adifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10103-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 10113-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 10123-amino-6-[3-({[(6-chloro-2-fluoro-3- Amethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 1013 3-amino-6-[3-({[(2-chloro-6-fluoro-3- Amethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 1014 3-amino-6-[3-({[(2-chloro-3,6- Adifluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10153-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10163-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,4- Atrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10173-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 10183-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10193-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2,6- Adifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10203-amino-N-[(3S)-azepan-3-yl]-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6- Aylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 10213-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2-chloro-6- Afluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10223-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,6- Adifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10233-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-4- Afluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10243-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2- Afluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10253-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10263-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-B N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10273-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10283-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3,4,5- Atrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10293-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10303-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,5- Atrifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 10313-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10323-amino-6-[3-({[(3-bromo-5-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-A [(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10333-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1H-pyrazol-1- Ayl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide 10343-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 10353-amino-6-[3-({[(2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)- Apiperidin-3-yl]pyrazine-2-carboxamide 10363-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10373-amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10383-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N- A[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10393-amino-6-[3-({[(3-methoxyphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-A piperidin-3-yl]pyrazine-2-carboxamide 10403-amino-6-{3-[({[phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-A yl]pyrazine-2-carboxamide 10413-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 10423-amino-6-{3-[({[3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-A N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide

Table 12 shows structure activity relationship data for selectedcompounds of the invention with respect to Chk1 and a number of otherenzymes, thus indicating selectivity of exemplary compounds of theinvention toward Checkpoint kinases, particularly Chk1. Inhibition isindicated as IC₅₀ with following key: A=IC₅₀ less than 50 nM, B=IC₅₀greater than 50 nM but less than or equal to 1000 nM, C=IC₅₀ greaterthan 1000 nM but less than 10,000 nM, and D=IC₅₀ of 10,000 nM or greater(a blank cell in the table indicates lack of data only).

Abbreviations for human enzymes listed in Table 12 are defined asfollows: EphB4 refers to ephrin-related receptor tyrosine kinase B4;Tie-2 refers to tyrosine kinase with immunoglobulin and EGF repeats;EGFR refers to epidermal growth factor receptor; FGFR1 refers tofibroblast growth factor receptor; KDR refers to kinase insert domaincontaining receptor; Flt1 refers to fms-like tyrosine kinase 1; fynrefers to proto-oncogene tyrosine-protein kinase fyn; and PDGFR-β refersto platlet derived growth factor receptor beta chain. Chk1 refers tocheckpoint homologue 1 (S. pombe); Chk2 refers to checkpoint-likeprotein 2; Flt1 refers to fms-like tyrosine kinase 1, Flt4 refers tofms-like tyrosine kinase 4; fyn refers to proto-oncogene tyrosineprotein kinase fyn; KDR refers to kinase insert domain containingreceptor; MAP4K3 refers to mitogen-activated protein kinase kinasekinase kinase 3; c-MET refers to the cellular homologue of the metproto-oncogene; CLK1 refers to CDC-like kinase1; EMK refers to ELKLmotif kinase 1; ErbB2 refers to erythroblastic leukemia viral Oncogenehomologue 2; IGFR1 refers to insulin-like growth factor receptor 1; IRKrefers to insulin receptor kinase; MAPKAP2 refers to mitogen-activatedprotein kinase-activated protein kinase; PKA refers to protein kinase A;PKC refers to protein kinase C epsilon isoform; PLK refers to polo-likekinase; scr refers to the src proto-oncogene; ZAP70 refers to zeta-chainassociated protein kinase, 70 kD; cdc2 refers to cell division cycleprotein 2.

TABLE 12 # Compound Chk1 Chk2 FGFR1 Flt1 Flt4 Fyn PDGFR-β KDR MAP4K3c-Met CLK1  1 3-amino-6-{3-[({[4- A A C B B C B B B C(methyloxy)phenyl]methyl} amino)carbonyl]phenyl}- N-[(3S)-piperidin-3-yyl]pyrazine-2- carboxamide  2 3-amino-N-[(3S)- A A C B A C B B A Cpiperidin-3-yl]-6-(3-{[({4- [(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl} phenyl)pyrazine-2- carboxamide  33-amino-6-[3-({[(4- A A C B A B B B A C chloro-2-fluorophenyl)methyl]amino} carbonyl)phenyl]-N- [(3S)-piperidin-3-yl]pyrazine-2- carboxamide  4 3-amino-6-{3-[({[4- A A C B B B B B B C(dimethylamino)phenyl]methyl} amino)carbonyl]phenyl}-N-[(3S)-piperidin-3- yl]pyrazine-2- carboxamide  5 3-amino-6-[3-({[(2,3-A A C B B B B B A B difluoro-4- methylphenyl)methyl]amino}carbonyl)phenyl]-N- [(3S)-piperidin-3- yl]pyrazine-2- carboxamide  63-amino-6-(3-{[(2,3- A A C B A C A B B C C dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl} phenyl)-N-[(3S)-piperidin- 3-yl]pyrazine-2-carboxamide  7 3-amino-6-[3-({[(4- A A C B A C B A A Cchlorophenyl)methyl]amino} carbonyl)phenyl]-N- [(3S)-piperidin-3-yl]pyrazine-2- carboxamide  8 3-amino-6-[3-({[(4- A A B B A B B B A Dfluorophenyl)carbonyl]amino} methyl)phenyl]-N- [(3S)-piperidin-3-yl]pyrazine-2- carboxamide  9 3-amino-6-[3-({[(4- A A B B A B A A A C Cchlorophenyl)carbonyl]amino} methyl)phenyl]-N- [(3S)-piperidin-3-yl]pyrazine-2- carboxamide 10 3-amino-6-(3-{[(4- A A B A A B A A A C Cchlorophenyl)acetyl]amino} phenyl)-N-[(3S)- piperidin-3-yl]pyrazine-2-carboxamide 11 3-amino-6-(3- A A B B A B B A A C{[(pentafluorophenyl)acetyl] amino}phenyl)-N- [(3S)-piperidin-3-yl]pyrazine-2- carboxamide 12 3-amino-6-(3-{[(2,4- A A B B A B A A A C Cdifluorophenyl)acetyl]amino} phenyl)-N-[(3S)- piperidin-3-yl]pyrazine-2-carboxamide 13 3-amino-6-[3- A A B B A B A A A D ({[(biphenyl-4-ylamino)carbonyl]amino} methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2- carboxamide 14 3-amino-6-(3-{[(4-bromo- A A BA A B A A A C C 2- fluorophenyl)carbonyl]amino} phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2- carboxamide 15 N-[3-(5-amino-6-{[(3S)- A A BA A B A A A B piperidin-3- ylamino]carbonyl}pyrazin-2-yl)phenyl]quinoline-3-carboxamide 16 3-amino-6-(3-{[(biphenyl- A A B BA B A A A C C 4- ylcarbonyl)amino]methyl} phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2- carboxamide 17 3-amino-N-[(3S)- A A B B A B A A A Dpiperidin-3-yl]-6-(3-{[(2- thienylcarbonyl)amino]methyl}phenyl)pyrazine-2- carboxamide 18 3-amino-6-(3-{[2- A A B B A B B B B C(ethylamino)ethyl]oxy}phenyl)- N-[(3S)-piperidin-3- yl]pyrazine-2-carboxamide 19 3-amino-6-[3-({[(1R,2S)- A A B B A B A A A D2-hydroxy-2,3-dihydro- 1H-inden-1- yl]amino}methyl)phenyl]-N-[(3S)-piperidin-3- yl]pyrazine-2- carboxamide # EGFR EMK EphA2R EphB4ErbB2 IGFR1 IRK MAPKAP2 PKA PKCe PLK SRC Tie-2 ZAP70 Cdc2  1 D D D C D DC D D D  2 D C D D D D C D C D  3 D C D C D D C D D D  4 D D D D C D D DD D  5 D C D C D D C D D D  6 D C C D D D C D D D C C C D  7 D C D C D DC D D D  8 C C C C D D C D D  9 C C C D D D C C C D B B C C 10 C C C D DD C C C D B B B C 11 C C D C D D C D D 12 B C C C C D D C C C D B B C D13 D C D C C D B D C 14 C C C D D D C C C C C C B D 15 C C D C D D C D D16 C C B D D D C B D C B C C C 17 C C D C D D C D D 18 C C C C D D D D D19 C B D C D D C D D

1. A compound of Formula I,

or a pharmaceutically acceptable salt thereof, wherein, R¹ is H; R² is Hand R³ is H or lower alkyl; R⁴ is —H or R⁵; R⁵ is selected from (1)lower alkyl; (2) aryl; (3) lower arylalkyl; (4) heterocyclyl; and (5)lower heterocyclylalkyl; or R⁴ and R⁵, when taken together with a commonnitrogen to which they are attached, form a five- to seven-memberedheterocyclyl, said five- to seven-membered heterocyclyl optionallycontaining at least one additional heteroatom selected from N, O, S, andP; Z is —N═; A is selected from —C(═O)—, —C(═S)—, —C(═NR⁶)—, and —R⁷,when A is —R⁷, E does not exist; R⁶ is selected from (1) —H; (2) —NO₂;(3) —N(R²)R³; (4) N(H)C(═NR²)N(R²)R³; (5) —CN; (6) —OR⁴; (7) loweralkyl; (8) heteroalicyclylalkyl; (10) arylalkyl; (11) alkoxy; and (12)heteroalicyclic; R⁷ is a five- to seven-membered heterocyclyl, saidfive- to seven-membered heterocyclyl optionally containing at least oneadditional heteroatom selected from N, O, S, and P; E is selected fromTable 2: TABLE 2

wherein each R¹⁶ is independently selected from (1); —H, (2) loweralkyl; (3) —CO₂R⁴, and (4) —C(═O)R⁴; or two of R¹⁶, together with thenitrogen or nitrogens to which they are attached, form a heterocyclicring; each R¹⁷ is independently selected from (1) —H; (2) halogen; (3)oxo; (4) —CN; (5) —NH₂; (6) —CF₃; (7) —NO₂; (8) —OR⁴; (9) —N(R⁴)R⁵; (10)—S(O)₀₋₂R⁵; (11) —SO₂N(R⁴)R⁵; (12) —CO₂R⁴; (13) —C(O)N(R⁴)R⁵; (14)—N(R⁴)SO₂R⁵; (15) —N(R⁴)C(O)R⁵; (16) —N(R⁴)CO₂R⁵; (17) —C(O)R⁴; (18)lower alkyl; (20) arylalkyl; (21) heterocyclyl; and (22) lowerheterocyclylalkyl; and R¹⁸ is lower alkyl; W is either (1) a six- toten-membered arylene or (2) a five- to ten-membered heteroarylene; X isselected from a single bond; —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₀₋₃—;—(CH₂)₀₋₃CO₂(CH₂)₀₋₃—; —(CH₂)₀₋₃SO₂N(R⁴)(CH₂)₀₋₃—; —N(R⁴)(CH₂)₂₋₃O—;—(CH₂)₀₋₃ N(R⁴)C(═O)N(R⁴)(CH₂)₀₋₃—; —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃O—;—(CH₂)₀₋₃S(O)₀₋₂(CH₂)₀₋₃—; —N(R⁴)(CH₂)₂₋₃N(R⁴)—;—(CH₂)₀₋₃C(=O)N(R⁴)(CH₂)₁₋₃C(═O)—; —(CH₂)₀₋₃OC(═O)N(R⁴)(CH₂)₀₋₃—;—C(═O)N(R⁴)N(R⁴)—; —(CH₂)₀₋₃CO₂(CH₂)₂₋₃N(R⁴)—;—(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃O—; —(CH₂)₀₋₃N(R⁴)(CH₂)₀₋₃—;—C(═O)N(R⁴)(CH₂)₂₋₃N(R⁴)—; —O(CH₂)₂₋₃O;—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃S(O)₀₋₂—;—(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃S(O)₀₋₂—; —(CH₂)₀₋₃O(CH₂)₀₋₃—; alkoxyl; andlower alkylene; and Y is selected from (1) lower alkyl substituted withone or more aryl; (2) aryl; (3) and heterocyclyl or Y is selected fromTable 1: TABLE 1

wherein each R¹⁵ is independently selected from (1) —H; (2) halogen; (3)—CN; (4) —NH₂; (5) —CF₃; (6) —NO₂; (7) —OR⁴; (8) —N(R⁴)R⁵; (9)—S(O)₀₋₂R⁵; (10) —SO₂N(R⁴)R⁵; (11) —CO₂R⁴; (12) —C(O)N(R⁴)R⁵; (13)—N(R⁴)SO₂R⁵; (14) —N(R⁴)C(O)R⁵; (15) —N(R⁴)CO₂R⁵; (16) —C(O)R⁴; (17)lower alkyl; (18) aryl; (19) lower arylalkyl; (20) heterocyclyl; and(21) lower heterocyclylalkyl.
 2. The compound according to claim 1,wherein R² and R³ are —H.
 3. The compound according to claim 2, whereinA is R⁷, and R⁷ is either

wherein each G¹ is independently ═N— or ═C(R¹¹)—, L is selected from—O—, —S(O)₀₋₂—, and —NR¹¹, wherein each R¹¹ is independently selectedfrom (1) —H, (2) halogen, (3) —CN, (4) —NH₂, (5) —CF₃, (6) —NO₂, (7)—OR⁴, (8) —N(R⁴)R⁵, (9) —S(O)₀₋₂R⁵, (10) —SO₂N(R⁴)R⁵, (11) —CO₂R⁴, (12)—C(O)N(R⁴)R⁵, (13) —N(R⁴)SO₂R⁵, (14) —N(R⁴)C(O)R⁵, (15) 2-N(R⁴)CO₂R⁵,(16) —C(O)R⁴, (17) lower alkyl (18) aryl; (19) lower arylalkyl; (20)heterocyclyl; and (21) lower heterocyclylalkyl.
 4. The compoundaccording to claim 3, wherein R⁷ is selected from

wherein R^(11a) is selected from —H, lower alkyl;

wherein each R¹² is independently selected from (1) —H, (2) halogen, (3)oxo, (4) —CN, (5) —NH₂, (6) —CF₃, (7) —NO₂, (8) —OR⁴, (9) —N(R⁴)R⁵, (10)—S(O)₀₋₂R⁵, (11) —SO₂N(R⁴)R⁵, (12) —CO₂R⁴, (13) —C(O)N(R⁴)R⁵, (14)—N(R⁴)SO₂R⁵, (15) —N(R⁴)C(O)R⁵, (16) —N(R⁴)CO₂R⁵, (17) —C(O)R⁴, (18)lower alkyl; (19) aryl; (20) lower arylalkyl; (21) Heterocyclyl; and(22) lower heterocyclylalkyl; R¹³ is selected from —H, and lower alkyl;Q is either ═N— or ═C(R¹²)—; and M is selected from —O—, —S(O)₀₋₂—, and—NR¹³.
 5. The compound according to claim 4, wherein W is

wherein each G² is independently ═N—or ═C(R¹⁴)—, and each R¹⁴ isindependently selected from (1) —H; (2) halogen; (3) —CN; (4) —NH₂; (5)—CF₃; (6) —NO₂; (7) —OR⁴; (8) —N(R⁴)R⁵; (9) —S(O)₀₋₂R⁵; (10)—SO₂N(R⁴)R⁵; (11) —CO₂R⁴; (12) —C(O)N(R⁴)R⁵; (13) —N(R⁴)SO₂R⁵; (14)—N(R⁴)C(O)R⁵; (15) —N(R⁴)CO₂R⁵; (16) —C(O)R⁴; (17) lower alkyl; (18)aryl; (19) lower arylalkyl; (20) heterocyclyl; and (21) lowerheterocyclylalkyl.
 6. The compound according to claim 5, wherein W is


7. The compound according to claim 6, wherein X is selected from (1)—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₀₋₃—; (2) —(CH₂)₀₋₃SO₂N(R⁴)(CH₂)₀₋₃—; (3)—N(R⁴)(CH₂)₂₋₃; (4) —(CH₂)₀₋₃N(R⁴)C(═O)N(R⁴)(CH₂)₀₋₃—; (5)—C(═O)N(R⁴)N(R⁴)—; (6) —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃O—; (7)—N(R⁴)(CH₂)₂₋₃N(R⁴)—; (8) —(CH₂)₀₋₃N(R⁴)(CH₂)₀₋₃; (9)—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₁₋₃C(═O)—; (10) —O(CH₂)₂₋₃O—; (11)—(CH₂)₀₋₃OC(═O)N(R⁴)(CH₂)₀₋₃—; (12) —(CH₂)₀₋₃O(CH₂)₀₋₃—; (13)—(CH₂)₀₋₃CO₂(CH₂)₂₋₃N(R⁴)—; (14) —(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃O—; (15)—C(═O)N(R⁴)(CH₂)₂₋₃N(R⁴)—; (16)alkoxyl and (17) lower alkylene.
 8. Thecompound according to claim 7, wherein X is selected from (1)—C(═O)N(H)(CH₂)₁₋₂—; (2) —(CH₂)₁₋₂C(═O)N(H)—; (3) —C(═O)N(H)—; (4)—SO₂N(H)(CH₂)₁₋₂—; (5) —(CH₂)₁₋₂SO₂N(H)—; (6) —SO₂N(H)—; (7)—N(H)C(═O)N(H)(CH₂)₁₋₂—; (8) —N(H)C(═O)N(H)—; (9)—(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—; (10) —(CH₂)₀₋₂O(CH₂)₀₋₂; (11) —C(═O)N(H)N(H)—;(12) —N(R⁴)(CH₂)₂₋₃N(R⁴)—; (13) —OCH₂C(═O)N(H)CH₂—; (14)—(CH₂)₁₋₂N(H)C(═O)N(H)—; (15) —OCH₂CH₂O—; —N(R⁴)CH₂C(═O)N(H)CH₂—; (16)—(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—; and (17) alkoxyl.
 9. The compoundaccording to claim 8, wherein Y is selected from phenyl; and a five- tosix-membered heterocyclyl.
 10. The compound according to claim 9,wherein R^(11b) is selected from (1) alkyl; (2) phenyl; (3) pyridyl; (4)morpholinyl; (5) pyrrolidinyl; (6) piperidinyl; and (7) azepanyl. 11.The compound according to claim 10, wherein R⁷ is


12. The compound according to claim 4, wherein R^(11b) is

wherein R¹⁴ is either —H or lower alkyl.
 13. The compound according toclaim 11, wherein R^(11b) is a pyridyl group.
 14. The compound accordingto claim 4, wherein R^(11b) is a pyridyl group bearing a 2-amino group.15. The compound according to claim 1, wherein A is —C(═O)— or—C(═NR⁶)—.
 16. The compound according to claim 15, wherein A is —C(═O)—.17. The compound according to claim 16 wherein W is

wherein each G² is independently ═N—or ═C(R¹⁴)—; wherein each R¹⁴ isindependently selected from (1) —H; (2) halogen; (3) —CN; (4) —NH₂; (5)—CF₃; (6) —NO₂; (7) —OR⁴; (8) —N(R⁴)R⁵; (9) —S(O)₀₋₂R⁵; (10)—SO₂N(R⁴)R⁵; (11) —CO₂R⁴; (12) —C(O)N(R⁴)R⁵; (13) —N(R⁴)SO₂R⁵; (14)—N(R⁴)C(O)R⁵; (15) —N(R⁴)CO₂R⁵; (16) —C(O)R⁴; (17) lower alkyl; (18)aryl; (19) lower arylalkyl; (20) heterocyclyl; and (21) lowerheterocyclylalkyl.
 18. The compound according to claim 17, wherein W is


19. The compound according to claim 18, wherein X is selected from—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃SO₂N(R⁴)(CH₂)₀₋₃,—N(R⁴)(CH₂)₂₋₃O, —(CH₂)₀₋₃N(R⁴)C(═O)N(R⁴)(CH₂)₀₋₃—, —C(═O)N(R⁴)N(R⁴)—,—(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₂₋₃O—, —N(R⁴)(CH₂)₂₋₃N(R⁴)—,—(CH₂)₀₋₃N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃C(═O)N(R⁴)(CH₂)₁₋₃C(═O)—,—O(CH₂)₂₋₃O—, —(CH₂)₀₋₃OC(═O)N(R⁴)(CH₂)₀₋₃—, —(CH₂)₀₋₃O(CH₂)₀₋₃—,—(CH₂)₀₋₃CO₂(CH₂)₂₋₃N(R⁴)—, —(CH₂)₀₋₃N(R⁴)C(═O)(CH₂)₀₋₃O—,—C(═O)N(R⁴)(CH₂)₂₋₃N(R⁴)—, alkoxyl, and lower alkylene.
 20. The compoundaccording to claim 19, wherein X is selected from —C(═O)N(H)(CH₂)₁₋₂—,—(CH₂)₁₋₂C(═O)N(H)—, —C(═O)N(H)—, —SO₂N(H)(CH₂)₁₋₂, —(CH₂)₁₋₂SO₂N(H)—,—SO₂N(H)—, —N(H)C(═O)N(H)(CH₂)₁₋₂—, —N(H)C(═O)N(H)—,—(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—, —(CH₂)₀₋₂O(CH₂)₀₋₂, —C(═O)N(H)N(H)—,—N(R⁴)(CH₂)₂₋₃N(R⁴)—, —OCH₂C(═O)N(H)CH₂—, —(CH₂)₁₋₂N(H)C(═O)N(H)—,—OCH₂CH₂O—, —N(R⁴)CH₂C(═O)N(H)CH₂—, —(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—,alkoxyl, and lower alkylene.
 21. The compound according to claim 20,wherein E is either


22. The compound according to claim 21, wherein E is either


23. The compound according to claim 22, wherein R² and R³ are —H. 24.The compound according to claim 15, wherein A is —C(═NR⁶)—.
 25. Thecompound according to claim 1, of formula II,

wherein E is selected from Table 7, TABLE 7

wherein each R¹⁶ is independently selected from (1); —H, (2) loweralkyl; (3) —CO₂R⁴, and (4) —C(═O)R⁴; or two of R¹⁶, together with thenitrogen or nitrogens to which they are attached, form a heterocyclicring; each R¹⁷ is independently selected from (1) —H; (2) halogen; (3)oxo; (4) —CN; (5) —NH₂; (6) —CF₃; (7) —NO₂; (8) —OR⁴; (9) —N(R⁴)R⁵; (10)—S(O)₀₋₂R⁵; (11) —SO₂N(R⁴)R⁵; (12)—CO₂R⁴; (13) —C(O)N(R⁴)R⁵; (14)—N(R⁴)SO₂R⁵; (15) —N(R⁴)C(O)R⁵; (16) —N(R⁴)CO₂R⁵; (17) —C(O)R⁴; (18)lower alkyl; (19) aryl; (20) arylalkyl; (21) heterocyclyl; and (22)lower heterocyclylalkyl; X is selected from —C(═O)N(H)(CH₂)₁₋₂—,—(CH₂)₁₋₂C(═O)N(H)—, —C(═O)N(H)—, —SO₂N(H)(CH₂)₁₋₂—, —(CH₂)₁₋₂SO₂N(H)—,—SO₂N(H)—, —N(H)C(═O)N(H)(CH₂)₁₋₂—, —N(H)C(═O)N(H)—,—(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—, —(CH₂)₀₋₂O(CH₂)₀₋₂, —C(═O)N(H)N(H)—,—N(R⁴)(CH₂)₂₋₃N(R⁴)——OCH₂C(═O)N(H)CH₂—, —(CH₂)₁₋₂N(H)C(═O)N(H)—,—OCH₂CH₂O, —N(R⁴)CH₂C(═O)N(H)CH₂—, —(CH₂)₀₋₁C(═O)N(H)(CH₂)₁₋₂C(═O)—,alkoxyl, and lower alkylene; each R²² is independently selected from (1)—H; (2) halogen; (3) oxo; (4) —CN; (5) —NH₂; (6) —CF₃; (7) —NO₂; (8)—OR⁴; (9) —N(R⁴)R⁵; (10) —S(O)₀₋₂R⁵; (11) —SO₂N(R⁴)R⁵; (12) —CO₂R⁴; (13)—C(O)N(R⁴)R⁵; (14) —N(R⁴)SO₂R⁵; (15) —N(R⁴)C(O)R⁵; (16) —N(R⁴)CO₂R⁵;(17) —C(O)R⁴; (18) lower alkyl; (19) aryl; (20) lower arylalkyl; (21)heterocyclyl; and (22) lower heterocyclylalkyl; Y is selected from Table8, TABLE 8

wherein each R¹⁵ is independently selected from (1) —H; (2) halogen; (3)oxo; (4) —CN; (5) —NH₂; (6) —CF₃; (7) —NO₂; (8) —OR⁴; (9) —N(R⁴)R⁵; (10)—S(O)₀₋₂R⁵; (11) —SO₂N(R⁴)R⁵; (12) —CO₂R⁴; (13) —C(O)N(R⁴)R⁵; (14)—N(R⁴)SO₂R⁵; (15) —N(R⁴)C(O)R⁵; (16) —N(R⁴)CO₂R⁵; (17) —C(O)R⁴; (18)lower alkyl; (19) aryl; (20) lower arylalkyl; (21) heterocyclylalkyl and(22) heterocyclylalkyl.
 26. The compound according to claim 1, offormula III,

wherein, each G is independently ═N—or ═C(R¹¹)—; L is selected from —O—,—S(O)₀₋₂—, and —NR¹¹; each R¹¹ is independently selected from (1) —H;(2) halogen; (3) —CN; (4) —NH₂; (5) —CF₃; (6) —NO₂; (7) —OR⁴; (8)—N(R⁴)R⁵; (9) —S(O)₀₋₂R⁵; (10) —SO₂N(R⁴)R⁵; (11) —CO₂R⁴; (12)—C(O)N(R⁴)R⁵; (13) —N(R⁴)SO₂R⁵; (14) —N(R⁴)C(O)R⁵; (15) —N(R⁴)CO₂R⁵;(16) —C(O)R⁴; (17) lower alkyl; X is selected from (1)—C(═O)N(H)(CH₂)₁₋₂—; (2) —(CH₂)₁₋₂C(═O)N(H)—; (3) —C(═O)N(H)—; (4)—SO₂N(H)(CH₂)₁₋₂—; (5) —(CH₂)₁₋₂SO₂N(H)—; (6) —SO₂N(H)—; (7)—N(H)C(═O)N(H)(CH₂)₁₋₂—; (8) —N(H)C(═O)N(H)—; (9)—(CH₂)₀₋₂N(R⁴)(CH₂)₀₋₂—; (10) —(CH₂)₀₋₂O(CH₂)₀₋₂; (11) —C(═O)N(H)N(H)—;(12) —N(R⁴)(CH₂)₂₋₃N(R⁴)—; (13) —OCH₂C(═O)N(H)CH₂—; (14)—(CH₂)₁₋₂N(H)C(═O)N(H)—; (15) —OCH₂CH₂O—; —N(R⁴)CH₂C(═O)N(H)CH₂—; (16)—(CH₂)₀₋₁ C(═O)N(H)(CH₂)₁₋₂C(O)—; (17) alkoxyl and (18) lower alkylene;Y is selected from Table 9, TABLE 9

wherein each R¹⁵ is independently selected from (1) —H; (2) halogen; (3)oxo; (4) —CN; (5) —NH₂; (6) —CF₃; (7) —NO₂; (8) —OR⁴; (9) —N(R⁴)R⁵; (10)—S(O)₀₋₂R⁵; (11) —SO₂N(R⁴)R⁵; (12) —CO₂R⁴; (13) —C(O)N(R⁴)R⁵; (14)—N(R⁴)SO₂R⁵; (15) —N(R⁴)C(O)R⁵; (16) —N(R⁴)CO₂R⁵; (17) —C(O)R⁴; (18)lower alkyl; (19) aryl; (20) lower arylalkyl; (21) heterocyclyl; and(22) lower heterocyclylalkyl; and each R²² is independently selectedfrom (1) —H; (2) halogen; (3) oxo; (4) —CN; (5) —NH₂; (6) —CF₃; (7)—NO₂; (8) —OR⁴; (9) —N(R⁴)R⁵; (10) —S(O)₀₋₂R⁵; (11) —SO₂N(R⁴)R⁵; (12)—CO₂R⁴; (13) —C(O)N(R⁴)R⁵; (14) —N(R⁴)SO₂R⁵; (15) —N(R⁴)C(O)R⁵; (16)—N(R⁴)CO₂R⁵; (17) —C(O)R⁴; (18) lower alkyl; (19) aryl; (20) lowerarylalkyl; (21) heterocyclyl; and (22) lower heterocyclylalkyl.
 27. Acompound selected from Table 10, or a pharmaceutically acceptable saltthereof: TABLE 10 Name3-amino-N,N-dimethyl-6-phenylpyrazine-2-carboxamide3-amino-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide3-amino-6-(4-fluorophenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[4-(ethyloxy)phenyl]pyrazine-2-carboxamide3-amino-6-[3-(ethyloxy)phenyl]pyrazine-2-carboxamide3-amino-6-{3-[(trifluoromethyl)oxy]phenyl}pyrazine-2-carboxamide3-amino-6-[3-(aminocarbonyl)phenyl]pyrazine-2-carboxamide6-[3-(acetylamino)phenyl]-3-aminopyrazine-2-carboxamide3-amino-6-[4-(dimethylamino)phenyl]pyrazine-2-carboxamide3-amino-6-(3-methylphenyl)pyrazine-2-carboxamide methyl3-[5-amino-6-(aminocarbonyl)pyrazin-2-yl]benzoate3-amino-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide3-amino-6-biphenyl-3-ylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(phenylmethyl)oxy]phenyl}pyrazine-2-carboxamide3-amino-6-(3-hydroxyphenyl)-N-methylpyrazine-2-carboxamide3-amino-N-[2-(methyloxy)ethyl]-6-phenylpyrazine-2-carboxamideN-[2-(acetylamino)ethyl]-3-amino-6-phenylpyrazine-2-carboxamide3-amino-6-phenylpyrazine-2-carbohydrazide3-amino-N-hydroxy-6-phenylpyrazine-2-carboxamide3-amino-6-[3-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[4-(ethyloxy)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-methylphenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[4-(methyloxy)phenyl]pyrazine-2-carboxamide3-amino-6-biphenyl-3-yl-N-methylpyrazine-2-carboxamide6-[3-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide3-amino-6-[3-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[4-(hydroxymethyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(1E)-N-methylethanimidoyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-[3-(methyloxy)phenyl]pyrazine-2-carboxamide3-amino-6-(4-fluoro-3-methylphenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-pyridin-3-ylpyrazine-2-carboxamide6-[4-(acetylamino)phenyl]-3-amino-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(methylamino)carbonyl]phenyl}pyrazine-2-carboxamide6-(3-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(5-methyl-1,2,4-oxadiazol-3-yl)pyrazine-2-carboxamide3-amino-6-[4-(dimethylamino)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{4-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide3-amino-6-(3,5-dimethylphenyl)-N-methylpyrazine-2-carboxamide6-(4-acetylphenyl)-3-amino-N-methylpyrazine-2-carboxamide3-amino-6-[3,4-bis(methyloxy)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(phenylcarbonyl)amino]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(methylsulfonyl)amino]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-[3-(1H-tetrazol-5-yl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-(aminocarbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(dimethylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[4-(methylsulfonyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-aminophenyl)-N-ethylpyrazine-2-carboxamide3-amino-6-[3-({[(4-fluorophenyl)amino]carbonyl}amino)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[4-(methyloxy)phenyl]amino}carbonyl)amino]phenyl}pyrazine-2-carboxamide6,6′-[(oxomethanediyl)bis(iminobenzene-3,1-diyl)]bis(3-amino-N-methylpyrazine-2-carboxamide)3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid3-amino-N-methyl-6-{3-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[methyl(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(4-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[3-(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[4-(methyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[3-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({(1R)-1-[4-(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[(3-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4-chlorophenyl)carbonyl]amino}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[1-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2,3-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[bis(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[ethyl(pyridin-4-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[4-(phenylmethyl)piperazin-1-yl]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[1-(phenylmethyl)piperidin-4-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(4-methylphenyl)carbonyl]amino}phenyl)pyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(5-methylpyrazin-2-yl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(pyridin-4-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[(furan-2-ylcarbonyl)amino]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(cyclohexylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(2-phenylpropyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[2-(2-chlorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({2-[2-(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[2-(2-thienyl)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-{3-[(cyclohexylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 1,1-dimethylethyl4-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)piperidine-1-carboxylate3-amino-N-methyl-6-(3-{[(piperidin-4-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-(5-phenyl-1,2,4-oxadiazol-3-yl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[5-(2-phenylethyl)-1,2,4-oxadiazol-3-yl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(1,1-dimethylethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(phenylamino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1R)-1-phenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1S)-1-phenylpropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(1R,2S)-2-phenylcyclopropyl]amino}carbonyl)phenyl]pyrazine-2-carboxamidephenylmethyl 4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoate3-amino-N-methyl-6-(4-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(4-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[4-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[4-({[(4-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-(4-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[3-(phenyloxy)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide3-amino-6-{3-[(diphenylacetyl)amino]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(phenylacetyl)amino]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(3-phenylpropanoyl)amino]phenyl}pyrazine-2-carboxamide 3-amino-N-methyl-6-(3-{[(1R)-1,2,3,4-tetrahydronaphthalen-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[3,4,5-tris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({(1R,2R)-2-[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({(1S,2S)-2-[(phenylmethyl)oxy]cyclopentyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-cyanophenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(cyclopentylcarbonyl)amino]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4-cyanophenyl)carbonyl]amino}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(phenylmethyl)amino]carbonyl}amino)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(naphthalen-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(tetrahydrofuran-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-6-{3-[({[3-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({2-[3,5-bis(methyloxy)phenyl]ethyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(2-phenylethyl)oxy]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[2-(4-methylpiperidin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({2-[4-(2-hydroxyethyl)piperidin-1-yl]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[2-(3-hydroxypyrrolidin-1-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({2-[ethyl(phenylmethyl)amino]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[2-(4-phenylpiperazin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({2-[methyl(phenylmethyl)amino]ethyl}oxy)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(2-morpholin-4-ylethyl)oxy]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({2-[(cyclopropylmethyl)(propyl)amino]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({2-[4-(phenylmethyl)piperidin-1-yl]ethyl}oxy)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(2-piperidin-1-ylethyl)oxy]phenyl}pyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[3-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({2-[4-(2-hydroxyethyl)piperazin-1-yl]ethyl}oxy)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl]oxy}phenyl)-N-methylpyrazine-2-carboxamide ethyl4-{2-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)oxy]ethyl}piperazine-1-carboxylate3-amino-N-methyl-6-[3-({[(3S)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[2-(phenyloxy)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({2-[4-(phenylmethyl)piperazin-1-yl]ethyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)piperidin-4-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(furan-3-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(furan-2-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[4-(phenylmethyl)morpholin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(6-fluoro-4H-1,3-benzodioxin-8-yl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(3,4-dichlorophenyl)acetyl]amino}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[4-(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(2-methylpropyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3-amino-N-methyl-6-(3-{[({3-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(cyclopropylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(4-methylphenyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[4-(methyloxy)phenyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide 3-amino-6-{3-[({[4-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3-amino-6-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-aminophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-pyrimidin-5-ylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-(methylsulfonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]pyrazine-2-carboxamide 3-amino-6-(4-hydroxyphenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[4-(aminosulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(4-chloro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide methyl3-{5-amino-6-[(cyclopropylamino)carbonyl]pyrazin-2-yl}benzoate methyl3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate3-amino-6-[3-({[(2,3-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[4-hydroxy-3-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2-(ethyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2-chloro-6-(phenyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-6-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(2,2-dimethylpropyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(cyclopentylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[2,4,6-tris(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(3-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[3,5-bis(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(2,2-diphenylethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-(3-thienyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylmethyl)amino]sulfonyl}phenyl)pyrazine-2-carboxamide5,5′-diamino-N,N′-dimethyl-2,2′-bipyrazine-6,6′-dicarboxamide3-amino-6-(1H-indol-5-yl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(2-thienyl)pyrazine-2-carboxamide3-amino-N-methyl-6-pyridin-4-ylpyrazine-2-carboxamide3-amino-N-cyclopropyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-cyclopropylpyrazine-2-carboxamide3-amino-N-ethyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-ethylpyrazine-2-carboxamide3-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(cyclopropylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4′-fluorobiphenyl-2-yl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2,3,4-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(9H-fluoren-9-ylamino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2-methylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(3,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(4-methylpiperazin-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(4-fluoro-3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2,4,6-trichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-6-[3-({[(2-chloro-6-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-3,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,3-difluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-6-[3-({[(6-chloro-2-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,5-difluorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-(3-{[(naphthalen-2-ylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylmethyl)thio]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylmethyl)sulfonyl]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylmethyl)oxy]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylmethyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide9H-fluoren-9-ylmethyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate phenylmethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- yl}phenyl)carbamateethyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate3-amino-6-[3-({[(3,4-dichlorophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 1,1-dimethylethyl(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2- yl}phenyl)carbamate(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl (3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbamate3-amino-6-[3-({[(4-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[({4-[(2-morpholin-4-ylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[2-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[(3-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-hydroxyphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(2-phenylhydrazino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-(2-hydroxyethyl)-6-(3-methylphenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(phenylacetyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(4-chlorophenyl)acetyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-6-{3-[({[2-chloro-5-(trifluoromethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamideN-[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)methyl]-1H-indole-2-carboxamide3-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(1H-indol-3-ylacetyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3-iodophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2-morpholin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[({3-[(2-morpholin-4-ylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(4-morpholin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(1-methylethyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[({[4-(1-methylethyl)phenyl]oxy}acetyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[({[(4-aminophenyl)thio]acetyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-(4-(methyloxy)-3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(5-{[(phenylmethyl)amino]carbonyl}pyridin-3-yl)pyrazine-2-carboxamide3-amino-6-[3-({[(4-iodophenyl)carbonyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(4-pentylphenyl)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(1,3-benzodioxol-5-ylcarbonyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[({1-[5-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(2-piperidin-1-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[2-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide1,1-dimethylethyl(3R)-3-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}pyrrolidine-1-carboxylate3-amino-N-methyl-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 3-{[(4-chlorophenyl)methyl]amino}-6-{3-[({(3R)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({(3R)-1-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamideN-methyl-3-({[3-(methyloxy)phenyl]methyl}amino)-6-(3-{[((3R)-1-{[3-(methyloxy)phenyl]methyl}pyrrolidin-3-yl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[({(3R)-1-[(2,6-dichlorophenyl)methyl]pyrrolidin-3-yl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamideN-methyl-3-[(phenylmethyl)amino]-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide 1,1-dimethylethyl3-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)pyrrolidine-1-carboxylate1,1-dimethylethyl 2-({[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)carbonyl]amino}methyl)pyrrolidine-1-carboxylate3-amino-N-methyl-6-(3-{[(pyrrolidin-3-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(pyrrolidin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(2-fluoro-5-{[(phenylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(1,3-benzodioxol-5-ylacetyl)amino]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(phenylmethyl)amino]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[({2-[(2-morpholin-4-ylethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(1-methylethyl)phenyl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[(4-butylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]carbonyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6-ylmethyl)amino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-amino-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(3,4-dihydro-2H-1,4-benzoxazin-6-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,5-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2-pyridin-4-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(2-pyridin-3-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(2,2-diphenylethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-3-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[3-(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[(4-aminophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[4-(phenyloxy)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[5-({[(2,6-difluorophenyl)methyl]amino}carbonyl)pyridin-3-yl]-N-methylpyrazine-2-carboxamide3-amino-6-(5-{[(biphenyl-2-ylmethyl)amino]carbonyl}pyridin-3-yl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(2-piperidin-1-ylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-{3-[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[6-(trifluoromethyl)pyridin-3-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-(1H-benzimidazol-2-yl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(2-phenylethyl)amino]phenyl}pyrazine-2-carboxamide3-amino-6-(5-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}pyridin-3-yl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[2-(phenylamino)ethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-ethylphenyl)methyl]amino}carbonyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(4-pyridin-3-ylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-(1,3-dihydro-2H-isoindol-2-ylmethyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1R)-1-phenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide 3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({[3-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-{3-[({[3-(trifluoromethyl)phenyl]methyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1S)-1-phenylethyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide methyl(2S)-{[(3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}phenyl)methyl]amino}(phenyl)ethanoate3-amino-6-(3-{[2-(2,5-difluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[2-(2,3,5,6-tetrafluoro-4-methylphenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[2-(2-fluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[2-(2,4-difluorophenyl)hydrazino]carbonyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-(3-{[2-(2,3,5,6-tetrafluorophenyl)hydrazino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(5-methylpyrazin-2-yl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(3S)-1-(phenylmethyl)pyrrolidin-3-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(3R)-1-(phenylmethyl)pyrrolidin-3-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[ethyl(phenylmethyl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(1S,2S)-2-phenylcyclopropyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-Amino-6-(3-benzylcarbamoyl-phenyl)-pyrazine-2-carboxylic acidmethylamide3-amino-N-methyl-6-[3-(4-phenyl-1H-imidazol-2-yl)phenyl]pyrazine-2-carboxamide 3-amino-N-methyl-6-[3-({[(4-propylphenyl)methyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(5-bromo-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(2R)-1,2,3,4-tetrahydronaphthalen-2-ylamino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(1-methyl-1-phenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[(9H-fluoren-9-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(naphthalen-1-ylamino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-[3-({[(3-fluorobiphenyl-4-yl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2-fluoro-4-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2-fluoro-4-furan-2-ylphenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[(naphthalen-2-ylamino)methyl]phenyl}pyrazine-2-carboxamide 3-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(2S)-1,2,3,4-tetrahydronaphthalen-2-ylamino]methyl}phenyl)pyrazine-2-carboxamide methyl3-amino-6-(3-{[(4,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxylate3-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({[2-fluoro-5-(2-thienyl)phenyl]methyl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(4-ethenyl-2-fluorophenyl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4,7-difluoro-3-methyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1S,2R)-2-(methyloxy)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(5-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2R)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(5-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(2S)-5-bromo-2,3-dihydro-1H-inden-2-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4-fluoro-1-hydroxy-2,3-dihydro-1H-inden-2-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1R,2S)-2-(methyloxy)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(4,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(3-oxo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(5-furan-2-yl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(6-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(5-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(5-furan-3-yl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[5-(3-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(1S)-4-fluoro-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(1S)-5,7-difluoro-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(6-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4,6-dichloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide3-amino-6-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(1S)-5-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(5-phenyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(4-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(4-phenyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[4-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[6-(2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[5-(4-methyl-2-thienyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[(2R)-6-phenyl-1,2,3,4-tetrahydronaphthalen-2-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-N-methyl-6-naphthalen-2-ylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({(1S,2S)-2-[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-{3-[(cyclopentylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-(3-{[(7-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-quinolin-3-ylpyrazine-2-carboxamide3-amino-6-[3-(1H-imidazol-1-ylmethyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({5-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({(1R,2R)-2-[(phenylmethyl)oxy]cyclopentyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)methyl]phenyl}-N-methylpyrazine-2-carboxamide3-amino-6-{3-[({5-[(cyanomethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}-N-methylpyrazine-2-carboxamide2-amino-5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-methylpyridine-3-carboxamide3-amino-N-methyl-6-[3-({[5-(4-methylphenyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[2-(dimethylamino)-1-phenylethyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-[3-({[5-(1H-1,2,4-triazol-1-yl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(5-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{3-[({4-[(2-morpholin-4-ylethyl)oxy]-2,3-dihydro-1H-inden-1-yl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(4-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-N-methyl-6-{1-[(phenylmethyl)amino]isoquinolin-7-yl}pyrazine-2-carboxamide 3-amino-N-methyl-6-(3-{[(2-morpholin-4-yl-1-phenylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-methyl-6-(3-{[(1-phenyl-2-pyrrolidin-1-ylethyl)amino]methyl}phenyl)pyrazine-2-carboxamide2-amino-5-(3-{[(6-bromo-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide2-amino-5-(3-{[(4,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide2-amino-5-(3-{[(7-bromo-4-fluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide2-amino-5-(3-{[(4-chloro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide2-amino-5-(3-{[(5,6-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide2-amino-5-(3-{[(5,7-difluoro-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyridine-3-carboxamide3-amino-6-{1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]isoquinolin-7-yl}-N-methylpyrazine-2-carboxamide3-amino-6-{3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,3-dihydro-1H-inden-5-yl}-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[6-(3-hydroxypropyl)-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(1,3-oxazol-5-yl)pyrazin-2-amine3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carbohydrazide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide1-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-yl]ethanone3-amino-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)methyl]phenyl}-N-(naphthalen-2-ylmethyl)pyrazine-2-carboxamide3-amino-N-cyclohexyl-6-{3-[(2,3-dihydro-1H-inden-1-ylamino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(pyridin-4-ylmethyl)pyrazine-2-carboxamide{3-[5-amino-6-(4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4H-1,2,4-triazol-3-yl)pyrazin-2-amine3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2,2,2-trifluoroethyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(5-hydroxypentyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(4-hydroxybutyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-pyrrolidin-1-ylethyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-piperidin-1-ylethyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-morpholin-4-ylethyl)pyrazine-2-carboxamide3-amino-N-(cyclopropylmethyl)-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino}methyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(phenylmethyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-phenylethyl)pyrazine-2-carboxamide[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-yl](phenyl)methanone3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(2-hydroxyethyl)pyrazine-2-carboxamide3-amino-N-cyclopropyl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(pyrrolidin-1-ylcarbonyl)pyrazin-2-amine{3-[5-amino-6-(5-methyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol{3-[5-amino-6-(5-phenyl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol(3-{5-amino-6-[5-(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N′-methylpyrazine-2-carbohydrazide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N,N-dimethylpyrazine-2-carboxamide5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(phenylmethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(dimethylamino)ethyl]pyrazine-2-carboxamide5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-phenyl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[2-(methylamino)ethyl]pyrazine-2-carboxamide3-{5-amino-6-[(3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-hydroxypropyl)pyrazine-2-carboxamide 1,1-dimethylethyl4-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate 1,1-dimethylethyl 4-[({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]piperidine-1-carboxylate3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-piperidin-4-ylpyrazine-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-(piperidin-4-ylmethyl)pyrazine-2-carboxamide3-[5-amino-6-(morpholin-4-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide1,1-dimethylethyl 3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-pyrrolidin-3-ylpyrazine-2-carboxamide(3-{5-amino-6-[5-(1,1-dimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol{3-[5-amino-6-(5-furan-2-yl-4H-1,2,4-triazol-3-yl)pyrazin-2-yl]phenyl}methanol[3-(5-amino-6-{5-[3-(methyloxy)phenyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)phenyl]methanol2-({3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2-yl}carbonyl)-N-phenylhydrazinecarboxamide3-{5-amino-6-[(4-methylpiperazin-1-yl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-(5-amino-6-{[4-(4-fluorophenyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-(5-amino-6-{[4-(phenylmethyl)piperazin-1-yl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide methylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glycinateN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glycine3-{5-amino-6-[(3,5-difluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-[5-amino-6-(biphenyl-4-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide{3-[5-amino-6-(3-pyridin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol(3-{5-amino-6-[3-(4-chlorophenyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1,1-dimethylethyl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine(3-{5-amino-6-[3-(2-thienyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[3-(methyloxy)phenyl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(dimethylamino)propyl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(1H-imidazol-1-yl)propyl]pyrazine-2-carboxamide3-{5-amino-6-[(4-chloro-3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-(5-amino-6-{[2,4-bis(methyloxy)phenyl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-(5-amino-6-{[4-(dimethylamino)phenyl]carbonyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide methyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-L-prolinate methyl1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidine-3-carboxylate 1,1-dimethylethyl 4-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperazine-1-carboxylate3-[5-amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-yl]-N-(phenylmethyl)benzamideN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}glutamic acid5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{5-[(methyloxy)methyl]-4H-1,2,4-triazol-3-yl}pyrazin-2-amine5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[3-(methylamino)propyl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-(3-pyrrolidin-1-ylpropyl)pyrazine-2-carboxamide3-(5-amino-6-{(1E)-N-[4-(methyloxy)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-(5-amino-6-{(1E)-N-[4-(1-methylethyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-1,3-benzothiazol-2-ylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-(4-methylphenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-(4-chlorophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-methyl-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-(2-hydroxyethyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide{3-[5-amino-6-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol{3-[5-amino-6-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol3-[5-amino-6-(2-aminopyrimidin-4-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-{5-amino-6-[2-(dimethylamino)pyrimidin-4-yl]pyrazin-2-yl}-N-(phenylmethyl)benzamide ethylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-L-tyrosinateN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}-D-tyrosine 1,1-dimethylethyl [3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)propyl]carbamate 3-amino-N-(3-aminopropyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidine-3-carboxylic 1,1-dimethylethyl[2-({[3-amino-6-(3- {[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)ethyl]carbamate 3-amino-N-(2-aminoethyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide1,1-dimethylethyl (1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}piperidin-4-yl)carbamate3-{5-amino-6-[(4-aminopiperidin-1-yl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[imino(2-phenylhydrazino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[imino(morpholin-4-ylamino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-(5-amino-6-{imino[(4-methylpiperazin-1-yl)amino]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-{5-amino-6-[imino(piperidin-1-ylamino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(azepan-1-ylamino)(imino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[imino({(2R)-2-[(methyloxy)methyl]pyrrolidin-1-yl}amino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide{3-[5-amino-6-(3-piperidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol3-{5-amino-6-[(1E)-N-morpholin-4-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide4-((2E)-2-{1-[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]ethylidene}hydrazino)benzoic acid ethyl((2E)-2-{1-[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]ethylidene}hydrazino)acetate3-{5-amino-6-[(1E)-N,N-dimethylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-(5-amino-6-{(1E)-N-[4-(methylsulfonyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-(4-cyanophenyl)ethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-pyridin-2-ylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-(5-amino-6-{(1E)-N-[amino(imino)methyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide 3-[5-amino-6-((1E)-N-{4-[(trifluoromethyl)oxy]phenyl}ethanehydrazonoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-(5-Amino-6-{1-[(4-nitro-phenyl)-hydrazono]-ethyl}-pyrazin-2-yl)-N-benzyl-benzamide 3-(5-amino-6-{(1E)-N-[4-(trifluoromethyl)pyrimidin-2-yl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-1H-1,2,3-benzotriazol-1-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-methylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine3-(5-amino-6-{(1E)-N-[4-(trifluoromethyl)phenyl]ethanehydrazonoyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-phenylethanehydrazonoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-(4-methylpiperazin-1-yl)ethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide{3-[5-amino-6-(3-pyrrolidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamideN-[3-(acetylamino)propyl]-3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-{3-[(furan-2-ylcarbonyl)amino]propyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-4-ylcarbonyl)amino]propyl}pyrazine-2-carboxamideN-[3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)propyl]quinoxaline-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[3-({[6-(trifluoromethyl)pyridin-3-yl]carbonyl}amino)propyl]pyrazine-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(quinolin-8-ylsulfonyl)amino]propyl}pyrazine-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{3-[(pyridin-2-ylsulfonyl)amino]propyl}pyrazine-2-carboxamide3-amino-N-[3-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)propyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-[5-amino-6-(2-methylpyrimidin-4-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-{5-amino-6-[2-(methylamino)pyrimidin-4-yl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-4-ylcarbonyl)amino]ethyl}pyrazine-2-carboxamide3-amino-N-{2-[(furan-2-ylcarbonyl)amino]ethyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamideN,N′-cyclohexane-1,2-diylbis[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide]N-[2-(acetylamino)ethyl]-3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(quinolin-8-ylsulfonyl)amino]ethyl}pyrazine-2-carboxamideN-[2-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)ethyl]quinoxaline-2-carboxamide3-amino-N-(2-{[(2-chloropyridin-3-yl)carbonyl]amino}ethyl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{2-[(pyridin-2-ylsulfonyl)amino]ethyl}pyrazine-2-carboxamide3-amino-N-[2-({[(3,5-dimethylisoxazol-4-yl)amino]carbonyl}amino)ethyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-[5-amino-6-(imino{2-[4-(trifluoromethyl)pyrimidin-2-yl]hydrazino}methyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-{5-amino-6-[[2-(1,3-benzothiazol-2-yl)hydrazino](imino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-[5-amino-6-(1,5-diphenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-[5-amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-[5-amino-6-(1-methyl-5-phenyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-[5-amino-6-((1E)-N-{(2R)-2-[(methyloxy)methyl]pyrrolidin-1-yl}ethanimidoyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-{5-amino-6-[(1E)-N-azepan-1-ylethanimidoyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-(5-amino-6-{(E)-[(phenylmethyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-[5-amino-6-((E)-{[amino(imino)methyl]hydrazono}methyl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-(5-amino-6-{(E)-[(2-hydroxyethyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-{5-amino-6-[(E)-(pyridin-2-ylhydrazono)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-(5-amino-6-{(E)-[(4-cyanophenyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-(5-amino-6-{(E)-[(4-methylphenyl)hydrazono]methyl}pyrazin-2-yl)-N-(phenylmethyl)benzamide3-{5-amino-6-[(E)-(hydroxyimino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide{3-[5-amino-6-(3-pyridin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol5-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-piperidin-3-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine3-amino-N-[3-({[4-(dimethylamino)phenyl]carbonyl}amino)propyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide 1,1-dimethylethyl4-[(3S)-3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]piperidine-1-carboxylate3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-piperidin-4-ylpyrrolidin-3-yl]pyrazine-2-carboxamide 1,1-dimethylethyl(2R)-2-{[(3S)-3-({[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidin-1-yl]methyl}pyrrolidine-1-carboxylate3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-{(3S)-1-[(2R)-pyrrolidin-2-ylmethyl]pyrrolidin-3-yl}pyrazine-2-carboxamide3-amino-N-((3S)-1-{[4-(dimethylamino)phenyl]methyl}pyrrolidin-3-yl)-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-{2-[({[4-(dimethylamino)phenyl]amino}carbonyl)amino]ethyl}-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-[2-({[4-(dimethylamino)phenyl]carbonyl}amino)ethyl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-{5-amino-6-[imino(2-pyridin-2-ylhydrazino)methyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide3-[5-amino-6-(morpholin-4-ylmethyl)pyrazin-2-yl]-N-(phenylmethyl)benzamideethyl 1-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]methyl}piperidine-4-carboxylate3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)-N-[(3S)-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]pyrazine-2-carboxamide methylN-{[3-amino-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}threoninate{3-[5-amino-6-(3-piperidin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol 3-(ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-[5-amino-6-(1-methyl-5-piperidin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-[5-amino-6-(5-methyl-1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide{3-[5-amino-6-(3-morpholin-2-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-yl]phenyl}methanol5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-{3-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-3-(ethylamino)-N-[(3S)-1-ethylpyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate3-amino-6-[3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1R)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1S)-1-phenylethyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-{5-amino-6-[(2-ethylhydrazino)(imino)methyl]pyrazin-2-yl}-N-(2,3-dihydro-1H-inden-1-yl)benzamide3-{5-amino-6-[imino(2-methylhydrazino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide3-{5-amino-6-[imino(2-phenylhydrazino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate phenylmethyl3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyrazin-2-amine[3-(5-amino-6-{3-[(3R)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methanol[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methanol3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide1,1-dimethylethyl 3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-(1-ethylpiperidin-3-yl)pyrazine-2-carboxamide3-amino-N-[(3S)-1-ethylpyrrolidin-3-yl]-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide(3-{5-amino-6-[5-(1-ethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-yl}phenyl)methanol5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[5-(1-ethylpiperidin-3-yl)-4H-1,2,4-triazol-3-yl]pyrazin-2-amine3-[5-amino-6-(1-ethyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzamide3-[5-amino-6-(1-methyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide(3-{5-amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-amine1,1-dimethylethyl (3S)-3-{[(3-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate3-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-pyrrolidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[(2,3-dihydro-1H-inden-2-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-{5-amino-6-[imino(2-pyridin-4-ylhydrazino)methyl]pyrazin-2-yl}-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzamide phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-ethyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate3-amino-6-(3-{(1S)-1-[(1S)-2,3-dihydro-1H-inden-1-ylamino]ethyl}phenyl)-N-methylpyrazine-2-carboxamide3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide1,1-dimethylethyl (3S)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrrolidine-1-carboxylate3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide phenylmethyl(3R)-3-{3-[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]-1-methyl-1H-1,2,4-triazol-5-yl}piperidine-1-carboxylate3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[(3,4-dihydro-2H-chromen-4-ylamino)carbonyl]phenyl}pyrazin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylate3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(pyridin-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(pyridin-3-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide dimethyl5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzene-1,3-dicarboxylate3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3R)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-piperidin-3-ylpyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[2-(1H-imidazol-4-yl)ethyl]pyrazine-2-carboxamide3-amino-N-azepan-4-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide 1,1-dimethylethyl(3S)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate 1,1-dimethylethyl4-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)azepane-1-carboxylate3-[5-amino-6-(5-{2-[(phenylmethyl)oxy]ethyl}-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-4-fluorophenyl)-N-methylpyrazine-2-carboxamide3-[5-amino-6-(1-phenyl-5-piperidin-3-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide3-{5-amino-6-[amino(imino)methyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]benzamide 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate3-amino-6-{3-[(3,4-dihydro-2H-chromen-4-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[(2,3-dihydro-1-benzofuran-3-ylamino)carbonyl]phenyl}-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3R)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide1,1-dimethylethyl4-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]azepane-1-carboxylate3-amino-N-azepan-4-yl-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-azepan-4-yl-6-{3-[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2-d][1,3]oxazol-2-yl]phenyl}pyrazine-2-carboxamide 1,1-dimethylethyl(3R)-3-[({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)methyl]pyrrolidine-1-carboxylate3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide 1,1-dimethylethyl(3R)-3-{[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]methyl}pyrrolidine-1-carboxylate3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-ylmethyl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-5-fluorophenyl)-N-methylpyrazine-2-carboxamide3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-[(methyloxy)carbonyl]benzoic acid methyl3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-5-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}benzoate5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-N′-pyrrolidin-3-ylbenzene-1,3-dicarboxamide3-[5-amino-6-(5-phenyl-1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-(phenylmethyl)benzamide3-[5-amino-6-(5-methyl-1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 1,1-dimethylethyl(3R)-3-({[3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)piperidine-1-carboxylate1,1-dimethylethyl(3R)-3-[({3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-N′-[(3R)-pyrrolidin-3-yl]benzene-1,3-dicarboxamide(3-{5-amino-6-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}phenyl)methanol3-[5-amino-6-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate3-amino-6-(3-{[(1-methyl-1-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-methylpyrrolidin-3-yl]pyrazine-2-carboxamide 3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-pyrrolidin-3-yl]-6-(3-{[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]methyl}phenyl)pyrazine-2-carboxamideN-[3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)phenyl]-2-(2,4-dichlorophenyl)acetamide 1,1-dimethylethyl(3S)-3-({[3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)pyrazin-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate3-amino-6-(3-hydroxyphenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]sulfonyl}phenyl)-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-[5-amino-6-(1-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzamide3-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-pyrrolidin-3-yl]-6-[3-({[(2,3,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-{5-amino-6-[3-(1-methylpiperidin-3-yl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl}-N-[(2-chloro-6-fluorophenyl)methyl]benzamide3-amino-N-1-azabicyclo[2.2.2]oct-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(4-chloro-2-fluorophenyl)methyl]benzamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2-chlorophenyl)methyl]benzamide 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate 1,1-dimethylethyl(3S)-3-[({3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]pyrazin-2-yl}carbonyl)amino]pyrrolidine-1-carboxylate5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-3-(4-piperidin-3-yl-1,3-thiazol-2-yl)pyrazin-2-amine3-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-pyrrolidin-3-yl]pyrazine-2-carboxamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,6-difluorophenyl)methyl]benzamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2-chloro-6-fluorophenyl)methyl]benzamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,5-dichlorophenyl)methyl]benzamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(3,4-dichlorophenyl)methyl]benzamide3-amino-6-{3-[({[4-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 1,1-dimethylethyl(3S)-3-{[(3-amino-6-{3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]phenyl}pyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(2-fluorophenyl)methyl]benzamide3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(3-fluorophenyl)methyl]benzamide3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(4-fluorophenyl)methyl]benzamide3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(3-chlorophenyl)methyl]benzamide3-(5-amino-6-{5-[(3S)-piperidin-3-yl]-4H-1,2,4-triazol-3-yl}pyrazin-2-yl)-N-[(4-chlorophenyl)methyl]benzamide3-amino-6-[3-(aminomethyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-hydroxyphenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-(aminomethyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate3-amino-6-[3-({[(4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-4-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-5-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2-[(trifluoromethyl)oxy]phenyl}methyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[4-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(naphthalen-2-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[4-(dimethylamino)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(1,3-benzodioxol-5-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(2-thienyl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-{3-[({[2-(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[2,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,3-difluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[4-(methylsulfonyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(5-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[({[4-(methylthio)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(2,4-difluorophenyl)methyl]benzamide3-amino-6-(3-{[(1,2-diphenylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)-N-[(3,4-difluorophenyl)methyl]benzamide3-amino-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide methyl4-[({[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]carbonyl}amino)methyl]benzoate3-amino-6-[3-({[(4-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-bromo-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-bromophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[4-fluoro-2-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[2-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3R)-pyrrolidin-3-ylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(3R)-pyrrolidin-3-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-piperidin-1-ylethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(2-phenylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-methyloxy)ethyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-iodophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-chlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(4-chlorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(4-chlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2,6-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(pentafluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2-chloro-4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[4-(methylthio)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2,4-dichlorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[4-(4-chlorophenyl)-2-thienyl]carbonyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-bromophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(naphthalen-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[2-(4-phenylpiperazin-1-yl)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamideN-[(3-{5-amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-(4-bromophenyl)ureaN-[(3-{5-amino-6-[(3R)-piperidin-3-ylacetyl]pyrazin-2-yl}phenyl)methyl]-N′-naphthalen-2-ylurea3-amino-6-(3-{[(2,4-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2-yl}carbonyl)amino]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[4-(dimethylamino)naphthalen-1-yl]carbonyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4-(1,2,3-thiadiazol-5-yl)phenyl]carbonyl}amino)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[4-(dimethylamino)phenyl]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[(2-hydroxyethyl)oxy]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(3,4-dihydro-2H-1,5-benzodioxepin-7-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(quinolin-7-ylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(biphenyl-4-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(4-bromo-2-fluorophenyl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamideN-[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]quinoline-3-carboxamide3-amino-6-[3-({[6-(methyloxy)-1-benzofuran-3-yl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[4′-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[3,5-bis(trifluoromethyl)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[(2,4-difluorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({2-[(trifluoromethyl)oxy]phenyl}sulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide 3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({2-[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-(3-{[({[2-(methylthio)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[(3-bromo-5-methylphenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[(2-bromophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide5-[3-(aminomethyl)phenyl]-3-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-amine 3-amino-6-{3-[({[4-(4-methylpiperazin-1-yl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[2-(4-fluorophenyl)ethyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2-morpholin-4-ylethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2R)-pyrrolidin-2-ylmethyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2S)-pyrrolidin-2-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[(cyclopentylamino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4-[(trifluoromethyl)oxy]phenyl}amino)carbonyl]amino}methyl)phenyl]pyrazine-2-carboxamide 3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-{3-[({[4-(methyloxy)phenyl]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-4-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(furan-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,3-dihydro-1,4-benzodioxin-6-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1-benzofuran-5-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-thienylcarbonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamideN-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-2-chlorobenzamideN-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-chlorobenzamideN-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-iodobenzamideN-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-3,5-difluorobenzamideN-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-bromo-2-fluorobenzamideN-{[3-(5-amino-6-{3-[(3S)-piperidin-3-yl]-1H-1,2,4-triazol-5-yl}pyrazin-2-yl)phenyl]methyl}-4-bromo-2-chlorobenzamide3-[3-(2-aminopyridin-4-yl)-1H-1,2,4-triazol-5-yl]-5-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazin-2-amine3-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[2-(2-thienyl)-1,3-thiazol-4-yl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[5-(2-thienyl)pyridin-3-yl]carbonyl}amino)methyl]phenyl}pyrazine-2-carboxamide3-amino-6-{3-[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,4-dichloro-6-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(2-thienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-(3-{[(3-thienylsulfonyl)amino]methyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(4-chlorophenyl)sulfonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1,3-benzodioxol-5-ylamino)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[({[4-(methyloxy)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[(4-fluorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[2-(diethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[(2-morpholin-4-ylethyl)oxy]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-(methyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-(ethyloxy)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1,2,3-thiadiazol-4-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[2-(ethylamino)ethyl]oxy}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide phenylmethyl4-(2-{[3-(5-amino-6-{[(3S)-piperidin-3-ylamino]carbonyl}pyrazin-2-yl)phenyl]oxy}ethyl)piperazine-1-carboxylate 3-amino-6-(3-{[({[4-(dimethylamino)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-6-[3-({[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-{3-[({[(4-chlorophenyl)amino]carbonyl}amino)methyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-(3-methylphenyl)pyrazine-2-carboxamide3-amino-6-(3-{[(2-methylphenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[3-(trifluoromethyl)phenyl]acetyl}amino)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[4-(methyloxy)phenyl]acetyl}amino)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(6-methylpyridin-3-yl)carbonyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(3-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3-ylacetyl)amino]phenyl}pyrazine-2-carboxamide 3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[(pyridin-3-ylcarbonyl)amino]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(2,5-difluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(4-fluorophenyl)acetyl]amino}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[3-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-Amino-6-[3-({[5-(4-nitro-phenyl)-furan-2-carbonyl]-amino}-methyl)-phenyl]-pyrazine-2-carboxylic acid (3S)-piperidin-3-ylamide3-amino-6-[3-({[(3-hydroxypyridin-2-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(5-methylisoxazol-3-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-(3-{[(isoxazol-5-ylcarbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-methyl-1,2,3-thiadiazol-5-yl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,5-dichloro-3-thienyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(5-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[2-chloro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(4-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[2-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-{3-[({[2-fluoro-4-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,3-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,6-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3,5-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3,4-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(6-chloro-2-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide 3-amino-6-[3-({[(2-chloro-6-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-chloro-3,6-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,5-dichlorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,4-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,3-difluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-fluoro-4-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-(3-{[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2-chloro-6-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(2,6-difluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-4-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-[3-({[(3-chloro-2-fluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-chloro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[2,6-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(3,4,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(4-fluoro-3-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-[3-({[(2,3,5-trifluorophenyl)methyl]amino}carbonyl)phenyl]pyrazine-2-carboxamide3-amino-6-[3-({[(5-fluoro-2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-bromo-5-fluorophenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-piperidin-3-yl]-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide3-amino-6-(3-{[(biphenyl-3-ylmethyl)amino]carbonyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2-methylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3,5-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(2,4-dimethylphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-[3-({[(3-methoxyphenyl)methyl]amino}carbonyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[3,5-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-6-{3-[({[3,4-bis(methyloxy)phenyl]methyl}amino)carbonyl]phenyl}-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide3-amino-N-[(3S)-azepan-3-yl]-6-{3-[({[4-(1H-pyrazol-1-yl)phenyl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide.


28. A pharmaceutical composition comprising a compound according toclaim 1 and a pharmaceutically acceptable carrier.
 29. A compoundaccording to the following name:3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide, or a pharmaceutically acceptable saltthereof.
 30. A method of diminishing proliferation of a plurality ofcancerous cells in a patient, the method comprising administering to thepatient the compound as described in claim 1, and one or more cancertherapeutic agents.
 31. The method of claim 30, wherein the compound iscombined with a pharmaceutically acceptable carrier.
 32. The method ofclaim 30, wherein the cancer therpeutic agent is selected from the groupconsisting of a Topoisomerase I inhibitor, a Topoisomerase II inhibitor,an alkylating agent, a nitrogen mustard, an aziridine, an epoxide, analkyl sulfonate, a nitrosourea, an alkylating agent-steroid conjugate, aDNA damaging/binding agent, a Cisplatin, an antibiotic, ananthracycline, an anthracenedione, an antimetabolite, an antifolate, anucleic acid analog, a ribonucleic acid analog, a ribozyme, a Vincaalkaloid, a Taxane, an enzyme, a natural product, a kinase inhibitor, ahormone a hormones antagonist, and a biological response modifier. 33.The method of claim 30, wherein where the cancer therapeutic agentcomprises at least one of: Camptothecin, Topotecan, 9-Nitrocamptothecin,9-Aminocamptothecin, Karenitecin, Irinotecan, Etoposide, EtoposidePhosphate, Teniposide, Amsacrine, Razoxane, Dexrazoxane,Mechlorethamine, Cyclophosphamide, Ifosfamide, Chiorambucil, Melphalan,Thiotepa, Trenimon, Triethylenemelamine, Dianhydrogalactitol,Dibromodulcitol, Busulfan, dimethylsulfate, Chloroethylnitrosourea,BCNU, CCNU, Methyl-CCNU, Streptozotocin, Chlorozotocin, Prednimustine,Estramustine, Procarbazine, Dacarbazine, Hexamethylmelamine,Pentamethylmelamine, Temozolomide, Cisplatin, Carboplatin, Oxaliplatin,Bleomycin, Dactinomycin, Mithramycin, Mitomycin2 C, Daunorubicin,Doxorubicin, Epirubicin, Idarubicin, Methotrexate, Edatrexate,Trimethoprim, Nolatrexed, Raltitrexed, Hydroxyurea, 5-fluorouracil,Ftorafur, Capecitabine, Furtulon, Eniluracil, ara-C, 5-azacytidine,Gemeitabine, Mercaptopurine, Thioguanine, Pentostatin, antisense DNA,antisense RNA, an antisense DNAIRNA hybrid, a ribozyme, Vincristine,Vinblastine, Paclitaxel, Docetaxel, L-Asparaginase, a kinase inhibitor,Imatinib, Mitotane, Aminoglutethimide, Diethyistilbestrol, Ethinylestradiol, Tamoxifen, Anastrozole, Testosterone propionate,Fluoxymesterone, Flutamide, Leuprolide, Prednisone, Hydroxyprogesteronecaproate, Medroxyprogesterone acetate, Megestrol acetate and Interferonalfa.
 34. The method of claim 33, wherein where the cancer therapeuticagent is Gemcitabine.
 35. The method of claim 34, wherein where thecompound is3-amino-6-[3-({[(2,4-difluorophenyl)methyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2- carboxamide, or a pharmaceuticallyacceptable salt thereof.